Standalone broadside prints produced for inclusion in the special edition of Parenthesis 34: The Journal of the Fine Press book Association, Special Edition. Printed from Monotype composition type, originally cast by Neil Winter at Whittington Press for Double Daggers Journal, Summer 2017. The type was reformatted and reprinted in order to create a companion print to The Enemies of Books 1 (2017) which was included in Parenthesis 32: The Journal of the Fine Press book Association, Special Edition, Spring 2017.

The text of the piece:

I just burnt a book. I didn't hate the book. In fact it's one of my favourites and I hope you will bear with me whilst I tell you about what happened.
The book in question was a copy of William Blades' The Enemies of Books, first published by Trubner & Co., London in 1880. This work is considered to be 'the first systematic study of book and library destruction' with chapters providing a fascinating account of the destructive powers of fire, water, gas and heat, dust and neglect, ignorance and bigotry, the bookworm, other vermin, bookbinders, collectors and lastly, servants and children. Personable and characterfully written, The Enemies of Books draws on the author's own experience of biblioclasm, as well as varied historical sources, to discuss both how and why books are destroyed. Highlights include a page-by-page analysis of the progress of a bookworm through an incunable printed by P. Schoffer in 1477 and an immensely painful Victorian diatribe on the danger to personal libraries posed by the supposed 'feminine weakness' of 'an ingrained curiosity'.

Books lead to books. I first came across a reference to Blades' work in Fernando Baez's A Universal History of the Destruction of Books, 2004 (trans 2008) which I had been led to by Jean-Claude Carriere & Umberto Eco's This is Not the End of the Book, 2009 (trans 2011). I mention this little trail as it led me not only to The Enemies of Books but a glut of books published since the mid noughties focussing on the material nature of the book, the experience of reading a physical book and the perceived fragility of this form in the face of screen-based technology. This concentration of interest on the physical form of the book and its destruction seemed to me to coincide, unsurprisingly, with an interest from designers and advertisers in the aesthetics of Letterpress printing. The phenomenon of old looking, 'distressed' type as the face of a whole raft of marketable items seems to have reached its zenith in the Conservative Party Manifesto of 2010. This document, with its retro aesthetic, appeared to aim for a sense of stability after the recession of 2008 and a reassuringly 'authentic' voice to narrate our progress into the digital future.

My work has always engaged with a search for value inherent in the Letterpress process. Thus the combination of these twin themes—fragility of the physical book, and a perceived stability in material processes—got me thinking about how one might explore such a contradiction on the press. I was a bit unsure of where to start until I realised that Print On Demand books held an interesting way forward. I ordered two inexpensive copies of William Blades' book, choosing The Enemies of Books, as it seemed to epitomise the argument for the value of the material book. If these copies really were produced on my demand then would it be wrong to destroy them at will? As a safeguard to my conscience I donated one to a book charity and then set about burning the other. I didn't enjoy my book burning. Despite knowing that another could be produced on demand it felt very wrong. The thought of the red embers tracing around the black type of each word still brings a twinge of shame.

I set about producing an ink from the ashes and once the laborious grinding, milling, and mixing was over used this ink to produce one oversized facsimile of the front cover of my 1902 copy of the book. The result was striking: the colour of the ink a suitable sepia covering an area twelve times the size of the original cover with a satisfying satin sheen. On seeing the print a friend enquired as to whether he could display the work in an upcoming gallery show and I was pleased when it sold, safe in the knowledge that I could produce another 'on demand'. I hadn't, however accounted for my lack of experience in ink making and having made few notes on quantities and procedures used for the first print all subsequent attempts were consistently poor. By mid 2012 other projects had taken over and having faltered, my plan for an edition of the burnt book prints was put to one side.

This year however I was asked to produce an edition of 100 prints to be included in the special edition of Parenthesis, The Journal of the Fine Press Book Association. With no brief other than the work should be a little smaller than A4 the invitation provided a good excuse to try again to develop and share this work. In the intervening years my previous failure had clearly been working away on my mind, this time I was disciplined. I obtained a glass muller for consistent milling of the pigment and was guided in its use by a master etcher. I made trials using the ash from copy paper and laboured over notes on timings, quantities and desired consistency. Still far from an expert ink maker I'm happy with the new understanding I have of this most significant component of printing.

As for the print, each one is placed on a sheet of fine quality book paper cut to the same proportions as one page of the original with a reproduction of the cover printed at 1:1 scale in the position of the text block. The ink is a nihilistic sepia with a heavier, darker version picking out the title and author's name in Old Face type. In brief it is a reproduction of the cover of a book, without contents, about the destruction of books, printed via the destruction of a copy of the book produced in a supposedly materially inferior manner made possible by digital technologies which heighten the sense of value in materially rich 'authentic' production methods of the past. Got that? Good.

If you do come across one I hope that you'll find an exercise in destruction and creation charged with symbolism, anxiety, material and technology. If not, maybe the print will serve as a reminder of W. Blades' excellent The Enemies of Books, the beginning of whose conclusion reads:

"It is a great pity that there should be so many distinct enemies at work for the destruction of literature, and that they should so often be allowed to work out their sad end. Looked at rightly, the possession of any old book is a sacred trust, which a conscientious owner or guardian would as soon think of ignoring as a parent would of neglecting a child. An old book, whatever its subject or internal merits is truly a portion of the national history; we may imitate it and print it in fac-simile, but we can never exactly reproduce it; and as an historical document it should be carefully preserved."


Despite the importance of ice streaming to the evaluation of West Antarctic Ice Sheet (WAIS) stability, we know little about mid-to long term changes in grounding line migration, ice streaming and ice accumulation in the upper Institute Ice Stream (IIS) catchment. In this thesis ground penetrating radar (GPR) and airborne radio-echo sounding (RES) methods have been employed to investigate the subglacial topography, internal stratigraphy and Holocene flow regime of the upper IIS catchment, in and around Horseshoe Valley. High resolution step-andcollect mode GPR was employed to assess the continuity of a Blue Ice Area (BIA) horizontal ice core climate record at Patriot Hills, where analysis has revealed two unconformities in the otherwise conformable 30,000 year climate sequence. By combining these data with airborne RES returns and pre-existing ice sheet models it is suggested that these unconformities represent periods of erosion, occurring as the former ice surface was scoured by katabatic winds in front
of Liberty and Mable Hills. Snow_Blow simulations suggest that katabatic winds have scoured the leeward slopes of these mountain ranges for over 10,000 years. This temporal stability can account for the large volume of BI moraine deposits in Horseshoe Valley, where compressive
BI flows promote glacial erosion and near-surface debris entrainment through freeze-on processes at the ice/bed interface and compressive thrust faulting. By investigating thicker ice flows in the upper IIS catchment and the Evans Ice Stream, this thesis has also analysed debris entrainment mechanisms at depth, where clasts are incorporated into the ice flow by englacial
stratigraphic folding and shearing at the glacial thermal boundary, governed by spatial and temporal changes in ice flow, ice temperature and sediment availability. Mid-to long term changes in ice flow in the wider IIS catchment have been investigated from airborne RES transects, revealing internal layer buckling, and therefore former enhanced ice-sheet flow in three distinct tributaries of the IIS. Buckled ice layers throughout the slow flowing ice in the Independence Trough and the fast-flowing ice in the Ellsworth Trough suggest that enhanced ice flow through these topographically confined regions was the source of ice streaming and iceflow reconfiguration during the mid-to-late Holocene. Although buckled layers also exist within the slow-flowing ice of Horseshoe Valley, a thicker sequence of surface-conformable layers in the upper ice column suggests slowdown more than 4000 years ago, indicating that enhanced flow switch off here cannot be attributed to late-Holocene ice flow reorganisation. The dynamic nature of ice flow in the IIS and its tributaries suggests that ice stream switching and mass change may have been regular during the Holocene, and that these changes may characterise the decline of the WAIS in this area. These results have important implications for our understanding of ice-sheet dynamics and the response of the ice sheet to climate change and provides explanations for fluctuations in debris entrainment and transportation processes in
Antarctica.


In 2007 two former U.S. secretaries of state, a defense secretary, and a former senator wrote persuasively in the Wall Street Journal that the time had come to move seriously toward a nuclear-free world. Almost two years later, the Global Zero movement was born with its chief aim to rid the world of such weapons once and for all by 2030. But is it realistic or even wise to envision a world without nuclear weapons? More and more people seem to think so. Barack Obama has declared "America's commitment to seek the peace and security of a world without nuclear weapons." But that is easier said than done. Michael O'Hanlon places his own indelible stamp on this critical issue, putting forth a "friendly skeptic's case for nuclear disarmament." Calls to "ban the bomb" are as old as the bomb itself, but the pace and organization of nonproliferation campaigns have picked up greatly recently. The growing Global Zero movement, for example, wants treaty negotiations to begin in 2019. Would this be prudent or even feasible in a world that remains dangerous, divided, and unpredictable? After all, America's nuclear arsenal has been its military trump card for much of the period since World War II. Pursuing a nuclear weapons ban prematurely or carelessly could alarm allies, leading them to consider building their own weapons uthe opposite of the intended effect. O'Hanlon clearly presents the dangers of nuclear weapons and the advantages of disarmament as a goal. But even once an accord is in place, he notes, temporary suspension of restrictions may be necessary in response to urgent threats such as nuclear "cheating" or discovery of an advanced biological weapons program. To take all nuclear options off the table forever strengthens the hand of those that either do not make that pledge or do not honor it. For the near term, traditional approaches to arms control, including dismantling existing bomb inventories, can pave the way to make a true nonproliferation regime possible in the decades ahead.


The standard treatment for patients with metastatic colorectal cancer (mCRC) in the first- and second-line setting is generally chemotherapy, which can be augmented with vascular endothelial growth factor-targeted therapies and, for patients with KRAS wild-type status, epidermal growth factor receptor-targeted therapies. However, nearly all patients ultimately develop disease progression and require later lines of therapy. Traditionally, physicians recycled chemotherapy in the later lines, with many patients showing diminished or no response. However, the past several years have seen the introduction of 2 agents for patients with refractory mCRC entering the third-line setting. The multitargeted tyrosine kinase inhibitor regorafenib and the cytotoxic combination of trifluridine/tipiracil have demonstrated significant improvements in overall survival in patients with refractory mCRC. Although these agents do not seem to induce complete responses, they can lead to durable stable disease. Regorafenib and trifluridine/tipiracil differ in their safety profiles. Physicians and patients must be properly educated on how to recognize and mitigate adverse events. For regorafenib, a dose-escalating strategy improves tolerability without impacting efficacy. When sequencing these agents, physicians should consider patient characteristics, including comorbidities, prior adverse reactions to treatments, and overall performance status. Ongoing studies are further defining the role of regorafenib and trifluridine/tipiracil in the treatment of mCRC.


Software controllers of reactive systems are ubiquitous in situations where incorrectness has a high cost. In order to place trust in the software, strong guarantees of its functional correctness are required. Reactive synthesis can be used to automatically construct software to a specification and ensure correctness. The drawback is that synthesis is computationally hard and it is infeasible to synthesise a controller for many specifications. Synthesis is formalised as a game between the controller and its environment. In this thesis we consider safety specifications that define the winning condition of the game for the controller as never allowing the game to visit an error state. The usual approach for solving controller synthesis is to compute the set of all winning states in the system and construct a controller that never deviates from this set. The set may be very large so it is standard practice to represent sets of states symbolically as a relation over the variables of the system. Binary decision diagrams (BDDs) are an efficient data structure used to store and manipulate sets of states for synthesis. The drawback of this approach is that a set of states has only one representation as a BDD and in some cases it may be exponentially large in the number of variables. The state explosion of BDDs causes controller synthesis to be infeasible on specifications with no compact representation of the set of winning states. In this thesis I propose a synthesis algorithm that constructs an approximation of the set of safe states that is sufficient to show correctness of the controller. The algorithm constructs an abstraction of the game and searches for a candidate strategy for the controller. Counterexamples are used to refine the strategy until it is winning for the game abstraction. Similar to bounded model checking, a SAT solver is used to efficiently implement the search for a counterexample trace. When a strategy is found to be winning in the abstraction of the game an approximation of the states for which the strategy wins is extracted from the strategy via interpolation. The search continues by refining the abstraction until the approximation of winning states converges on a fixed point that is sufficient to prove that the specification is realisable.


Purpose: In forest insurance market, there are three main participants including the insurance company, the forest farmer and the government. As different participant has different benefit object, there will be a complex and dynamic game relationship among all participants. The purpose of this paper is to make the game relationship among all participants in forest insurance market clear, and then to put forward some policy suggestions on the implementation of forest insurance from the view of game theory. Design/methodology/approach: Firstly, the static game model between the insurance company and the forest farmer is set up. According to the result of static game model, it's difficult to implement forest insurance without government. Secondly, the tripartite dynamic game model among the government, the insurance company and the forest farmer is proposed, and the equilibrium solution of tripartite dynamic game model is acquired. Finally, the behavioral characteristics of all participants are analyzed according to the equilibrium solution of tripartite dynamic game model. Findings: the government's allowance will be an important positive factor to implement forest insurance. The loss of the insurance company, which the lower insurance premium brings, can be compensated by the allowance from the government. The more the government provides allowance, the more actively the insurance company will implement forest insurance at a low insurance premium. In this situation, the forest farmer will be more likely to purchase the forest insurance, then the scope of forest insurance implementation will expend. Originality/value: There is a complex and dynamic game relationship among all participants in forest insurance market. Based on the tripartite dynamic game model, to make the game relationship between each participant clear is conducive to the implementation of forest insurance market in China.


The letters of 1924 were written, for the most part, by persons who had received copies of Herbert David Croly's biography of Willard Straight, and many contain recollections of Straight's life. A few notes were originally addressed to Croly. The book was published in April in New York by The Macmillan Company, and the first edition was largely distributed among Straight's friends and acquaintances. Some names that appear on the reel are Corinne Robinson Alsop, Mabel Boardman, Fairman Rogers Dick, Louis Agassiz Fuertes, Herbert C. Hoover, Peter Augustus Jay, and Philip James McCook. The correspondence ends with two 1925 notes and a few undated items.
Next on the reel are a group of passports, appointments and other documents. These are followed by memoirs from forty persons. These vary in length from a paragraph quotation to a 41-page article, and most are typed copies. Excerpts from George Marvin's Mukden diary from 14 August to 28 December 1907 are followed by excerpts from Mrs. Straight's letters to Beatrice Bend from 2 October 1911 to 25 June 1912. Most of these were written in Peking.
The last portion of the reel is made up of articles written by Straight.


Optimal Dynamic Allocation between Taxable and Nontaxable Assets Zhidong Wang This dissertation studies the problem of dynamically trading between taxable and nontaxable assets in order to maximize the expected utility of terminal wealth. Some properties of the optimal solution are demonstrated and are applied to simplify the representation, analysis and computation of the optimal policy. In particular, the optimal policy can be simply described by one or two target lines in a two-dimensional state space. Here a target line is a curve that consists of the optimal target points on all trading tracks in a certain direction, and a trading track is a set of states with a common characteristic value. The analytical solution for the optimal policy just prior to the termination is also derived. Besides providing a reference for numerical solutions, it can be used throughout the whole time horizon as a good approximate optimal policy. Several numerical methods are developed for these problems. One method calculates expectation by solving partial differential equations (PDE), and two methods by applying simulation (using point-estimation and regression, respectively). The PDE-based method has the highest computational efficiency and provides the best solution, while the two simulation-based methods can also provide solutions which have investment performance very close to that of PDE-based method.


American constitutional law is dominated by four Constitutional Personae, who can be identified by their inclinations, their temperaments, their sensibilities, and their self-presentations. Indeed, many constitutional debates consist of stylized disagreements among the leading Personae: Heroes, Soldiers, Burkeans, and Mutes. Earl Warren is the iconic Hero; Oliver Wendell Holmes, Jr. is the iconic Soldier; Felix Frankfurter is the iconic Burkean; Alexander Bickel speaks for the Mute. At different times and places, and under different constitutional provisions, liberals and conservatives can be Heroes, Soldiers, Burkeans, or Mutes. While the appeal of one or another Persona undoubtedly has psychological and social sources, the choice of the appropriate Persona, in particular cases, should be a product of the proper theory of constitutional interpretation, which must in turn be chosen on the basis of pragmatic judgments about the magnitude and number of errors.


THE FOCUS OF the present paper is the American led victories in the cold war and in the North/South struggle, and the consequent reassertion of American hegemony. These are seen here as two conceptually distinguishable struggles, victories, and defeats. But the two--no matter from what angle they are viewed--are intertwined and mutually interacting. This is a logical hypothesis, one that will be tested in this study. The evidence used here to indicate the American led victories is ultimately traceable to roll calls of the General Assembly of the United Nations. The roll calls are the raw material used since 1984 by the United States mission to the United Nations to generate annual indices of concordance with the United States position for each member and also aggregated composite indices for key groups. Two indices have been generated for each member and for key groups. One type index features all roll calls for a session; the other type only the restricted number of roll calls for the session deemed important by the U.S. mission and on which the mission and even the U.S. embassies around the world lobbied. The publication of these two types of indices allows the researcher the rare opportunity to resolve a classical enigma in roll call analysis: how to distinguish between the reaction of the voter to the substance and content of a bill or a draft resolution versus the reaction of the voter to the impact of factions, parties, and other outside pressures impinging on the voter. The literature indicates that the voting on all roll calls should be used to indicate reaction to content and substance, that on roll calls deemed important and lobbied by the U.S. mission, the example in our case, should be used to measure the impact of U.S. pressure and therefore the presence of U.S. hegemony. In the case of the third world in this study, this pressure is visualized as being pitted against the opposing pressure associated with loyalty to the other members of the group. Each type index will be applied to both of the major struggles presented in the paper, and the findings will be duly recorded and interpreted. The U.S. Mission has published annually both types of indices, beginning in 1984, with the last one published in 1992 and applying to 1991. They thus span the cold war and post cold war period. This provides a unique opportunity to test what Tomlin calls the convergent validity of roll calls, the ability of these instruments to reflect "reality", i.e. the situation as it exists outside the halls of the world institution. In this case we know what happened to communism in 1989 and 1990 in the real world, and we shall examine the two types of indices which precede and which follow the death of communism. The fact that the changes for the former Soviet bloc were dramatic is significant for our purposes, since the paper is built upon the assumption of convergent validity. The paper provides other persuasive empirical evidence to support this type of validity before the mission's indices are examined. Both indices for the former Soviet bloc and those for the third world witness dramatic change in the post cold war period, but there is a significant difference in the changes. This will enable us to draw a distinction between the defeat of communism and the defeat of the South: the North/South struggle continues on as a substantive policy, but attenuated by increasing pressure from the United States. The impact which the defeat of communism had upon the third world will also be assessed. The defeat of the Southern states in "the real world" has been less obvious than that of communism, and their defeat will be discussed in the section which follows this introduction. The defeat of communism in the real world will be assumed, this struggle being too broad to fit within the parameters of the paper. The Southern defeat took place in the arena of political economy, and it will be discussed in the context of the oil shocks and the economic policies of the Reagan administration. …


Recognizing the importance of university and community partnerships to address social issues, a mentoring program was implemented on a juvenile justice campus (JJC). A collaborative effort between a regional hispanic-serving university, the county probation department, and a non-profit agency resulted in the development and implementation of a mentoring program with incarcerated youth. Students assisted in the development and implementation of the mentoring program which incorporated life skills development, violence prevention, financial planning, parenting groups, needs assessments, and meditation. Student perceptions of their experience are explored using qualitative research methods. Educational benefits, the importance of collaboration, and the relationship between self-efficacy and placement satisfaction are discussed.


Concurrent and reactive systems often exhibit multiple time scales. For instance, in a discrete simulation, the scale at which agents communicate might be very different from the scale used to model the internals of each agent.
 We propose an extension of the synchronous model of concurrency, called reactive domains, to simplify the programming of such systems. Reactive domains allow the creation of local time scales and enable refinement, that is, the replacement of an approximation of a system with a more detailed version without changing its behavior as observed by the rest of the program.
 Our work is applied to the ReactiveML language, which extends ML with synchronous language constructs. We present an operational semantics for the extended language and a type system that ensures the soundness of programs.


In-service training has been used as a certain procedure for improving service quality and developing staff knowledge and awareness. This study aimed to evaluate the in-service training climate in libraries located in northern Iran medical universities from their staff viewpoints with ClimateQual survey tool. As a cross-sectional and analytical-survey, this study conducted among all staff of northern Iran medical libraries –including Babol, Mazandaran (Sari), Golestan (Gorgan) and Gilan (Rasht)- in 2012. The research instrument included ClimateQual Questionnaire developed by Association of Research Libraries (ARL) in 2009 and normalized by the researcher in his PhD dissertation in 2011. The rank of in-service component among all 9 components of ClimateQual was 8 (10.24 ± 3.17). As result, in-service training climate was not satisfactory from the staff viewpoints. ANOVA test results showed that in-service status was somewhat similar quantitatively and qualitatively in the studied universities (Sig.=591). There was a significant difference between staff in-service training mean scores according to their educational degrees (Sig.= 0.006). It is necessary to revise deeply in the quality and quantity of staff inservice training in the studied libraries.


There is no effective method of homogeneity measurement of compost prism. The most frequently used technology is the examination of the particle distribution. This method needs a lot of time and large number of samples. The aim of our research is establishing different effective methods to determine the homogeneity of compost prisms. During our work, we examined the homogeneity of a prism made of sewage sludge and saw-dust mixture.The measurements were based on the different properties of raw materials. According to this we examined the homogeneity by moisture content, heavy metal content and gas distribution measurements.The most effective method is the measurement of gasconcentration. Although gas-concentration measurements it need special equipment it has more advantages than the other methods. The examination of gas-distribution compensates the problem of sampling because the measurement is direct. It provides the opportunity to estimate the amount of emitted toxic gases and to determine the maturity of the compost and the effectiveness of the degradation.


The objective of this work is to determine the state of the art of social innovation laboratories for the collaborative construction of knowledge from the perspective of open innovation. It employs the methodology of the systematic mapping of the literature using the Science Direct, Springer Open and Google Scholar academic databases. The most significant findings include a tendency for social innovation laboratories using different technologies to socialize knowledge and the use of collaboration tools for the collaborative construction of knowledge. Is has been found that the creation of citizen networks (open social networks, researcher networks or contributor networks) and interdisciplinary work groups is common. Experts in laboratories suggest participating in listening mode since they take into account the experience of those affected and non-experts. Therefore, social innovation labs are spaces that are open to proposals for designing a work plan involving a range of actors to prototype a proposal from the perspective of open innovation.


New technology has brought with it new tools for learning, and research has shown that the educational potential of video games resonates with scholars, teachers, and students alike. In Augmented Learning, Eric Klopfer describes the largely untapped potential of mobile learning games--games played on such handheld devices as cell phones, Game Boys, and Sony PSPs--to make a substantial impact on learning. Examining mobile games from both educational and gaming perspectives, Klopfer argues that the strengths of the mobile platform--its portability, context sensitivity, connectivity, and ubiquity--make it ideal for learning games in elementary, secondary, university, and lifelong education. Klopfer begins by exploring the past and present of education, educational technology, "edutainment," and mobile games, and then offers a series of case studies of mobile educational games that have been developed and implemented in recent years. These games--either participatory (which require interaction with other players) or augmented reality (which augment the real world with virtual information)--can be produced at lower cost than PC or full-size console games. They use social dynamics and real-world contexts to enhance game play, can be integrated into the natural flow of instruction more easily than their big-screen counterparts, and can create compelling educational and engaging environments for learners. They are especially well-suited for helping learners at every level develop twenty-first century skills--including the ability to tackle complex problems and acquire information in "just-in-time" fashion. All of this, Klopfer argues, puts mobile learning games in a unique and powerful position within educational technology.


This report presents an analysis of U.S. Patent No. 10,960,070 (the "'070 patent"), an important and new coronavirus vaccine patent owned by the U.S. government, along with two of the government's academic partners. The report concludes that the '070 patent appears to be valid, enforceable by the U.S. government, and infringed by Moderna, Inc. (Moderna), because Moderna is currently making and selling a COVID-19 vaccine — mRNA-1273 — that incorporates and relies on technology described and claimed by the '070 patent. Moderna does not appear to have the U.S. government's permission to use this patented technology. Because Moderna lacks permission to use the technology, because the technology is essential to mRNA-1273's function and value as a vaccine, and because mRNA-1273 has been a financial blockbuster for Moderna, the '070 patent provides the U.S. government significant leverage over Moderna. The U.S. government could assert the '070 patent against Moderna in court and could (assuming Moderna's continued financial success) demand hundreds of millions or even over a billion dollars in compensation. The U.S. government could alternatively use the threat of litigation of the '070 patent to bring Moderna back to the negotiation table and convince Moderna to share its own patents, trade secrets, and other intellectual property on mRNA-1273 with the U.S. government and with vaccine manufacturers around the world. The latter option is the better one, to accelerate scale-up of global mRNA vaccine manufacturing, vaccinate the world, and bring the COVID-19 pandemic to a conclusive end.


BACKGROUND
Pediatric patients' self-report of health-related quality of life (HRQOL) has emerged as an important patient-based health outcome. A practical, validated generic measure of HRQOL facilitates assessing risk, tracking health status, and measuring treatment outcomes in pediatric populations.

METHODS
The PedsQL is a brief, standardized, generic assessment instrument that systematically assesses patients' and parents' perceptions of HRQOL in pediatric patients with chronic health conditions using pediatric cancer as an exemplary model. The PedsQL is based on a modular approach to measuring HRQOL and consists of a 15-item core measure of global HRQOL and eight supplemental modules assessing specific symptom or treatment domains. The PedsQL was empirically derived from data collected from 291 pediatric cancer patients and their parents at various stages of treatment.

RESULTS
Both reliability and validity were determined. Cronbach's alpha coefficients for the core measure (alpha = .83 for patient and alpha = .86 for parent) were acceptable for group comparisons. Alphas for the patient self-report modules generally ranged from .70 to .89. Discriminant or clinical validity, using the known-groups approach, was demonstrated for patients on- versus off-treatments. The 11 scales showed small-to-medium positive intercorrelations, supporting the multidimensional measurement model. Further construct validity was demonstrated via a multimethod-multitrait matrix using standardized psychosocial questionnaires.

CONCLUSION
The results support the PedsQL as a reliable and valid measure of HRQOL. The PedsQL core and modular design makes it flexible enough to be used in a variety of research and clinical applications for pediatric chronic health conditions.


This paper draws on the extant literature and experiences of selected ACBF‐supported programs to interrogate approaches to enhancing institutional leadership in African universities. The paper posits that African universities must proactively take charge of fostering institutional leadership so as to translate leadership competence into strategic assets. Such assets are key to bolstering intellectual capital, strategic scanning, i.e. the capacity to recognize the behaviour of interconnected systems to make effective decisions under varying strategic and risk scenarios, and the transformation of knowledge. To this end, African universities need to transcend their current "modern" system of education to a post‐modern perspective, which recognizes context, collaboration and knowledge as valued skills. Enhancing institutional leadership is also crucial if Africa is to compete in today's rapidly globalizing world and knowledge society. More importantly, doing so has direct impact on shaping the quality of leadership on the Continent, and consequently the resulting policy decisions and governance. The paper concludes that while institutional, political, demographic as well as resource challenges exist, African universities today, are uniquely positioned as a result of uptake of knowledge management, strengthened private‐public partnerships and advances in ICT to enhance institutional leadership.


Siddharth Krishna Kumar1 and co-authors claim to have shown that "GCTA applied to current SNP data cannot produce reliable or stable estimates of heritability." Given the numerous recent studies on the genetic architecture of complex traits that are based on this methodology, these claims have important implications for the field. Through an investigation of the stability of the likelihood function under phenotype perturbation and an analysis of its dependence on the spectral properties of the genetic relatedness matrix, our study characterizes the properties of an important approach to the analysis of GWAS data and identified crucial errors in the authors' analyses, invalidating their main conclusions.


Different Au-Ag-Cu samples have been studied by mechanical spectroscopy. Both polycrystals and bi-crystals show a relaxation peak at 800 K, accompanied by an elastic modulus change. Since this peak is absent in single crystals it is related to the presence of grain boundaries. Molecular dynamics simulations reveal two microscopic mechanisms, when a shear stress is applied onto a Sigma 5 grain boundary: at 700 K, the boundary migrates perpendicularly to the boundary plane under an external stress. At 1000 K, only sliding at the boundary is observed. These two mechanisms acting in different temperature intervals are used to model the mechanic response of a polycrystal under an applied stress. The models yield expressions for the relaxation strength Delta and for the relaxation time tau as a function of the grain size. A comparison with the mechanical spectroscopy measurements of polycrystals and the bi-crystals show that the grain boundary sliding model reproduces correctly the characteristics of the grain boundary peak.


Graduate students in six online courses were asked to complete a questionnaire related to dimensions of engagement including participation and interaction, performance, studying, and relevance of material. Students were asked to indicate the importance of various online course features (e.g., online discussions) in enhancing their engagement in each dimension using a Likert scale. Twenty-six (29%) students completed the questionnaire. Students rated most course management system features as extremely important or very important. When the ratings for the four engagement areas were grouped by course site feature, the feature with the highest mean rating was "instructor feedback on assignments/assessments." The feature with the lowest mean rating was "online chats with other students." While the practices of the instructor in the courses studied may have influenced the students' perceptions, it is clear that students especially value contact with the instructor.


As an analytical and critical survey of Sibelius' symphonies and tone-poems, this study is designed to fill a significant gap in the research of this composer which hitherto has been primarily concerned with historical and musicological issues. Those analytical investigations which exist, typically as a supplement to more biographical concerns, have not made use of modern techniques nor are they comprehensive. Beyond this self-evident purpose of processing analytical findings, the thesis aims not only to demonstrate a symposium of Sibelius' compositional techniques but also to give a new perspective to these achievements. The layout and presentation of material has been designed to facilitate this dual purpose, dispensing with a mere catalogue of analyses in favour of grouping their findings into considerations of larger issues. Thus, Part I - 'The Symphonies' - reflects the layered analytical approach to each work in chapters which move from the general to the particular (Style, Form, Tonality, Thematic Process) selecting examples from the entire genre appropriate to each issue. The final chapter in this section concludes by synthesising those areas in a detailed analysis of a single work. Part II - 'The Tone-Poems' - opens with a more general discussion of the two genres in question revealing cChtrasts and consistencies. Thereafter, their survey divides into two apparently chronological sections, though in fact the distinction is a stylistic one and complements internal considerations of the symphonies themselves. The application of reductive, layered analysis appears to be new in this context and its findings reveal a more progressive compositional attitude than has previously been credited to a figure generally viewed as reactionary. Its evidence, notably in the areas of extended tonality and formal compression, suggests an historical placing for Sibelius within twentieth-century musical developments, indicating both his awareness of the problems facing composers of the period and his personal solutions. The final chapter discusses this essentially speculative topic, its more subjective standpoint balancing the analytical objectivity which constitutes the majority of the thesis. Its conclusion is modest: Sibelius as neither reactionary nor revolutionary, but, nevertheless, progressive.


Two computational systems created by Vicky Isley & Paul Smith (aka boredomresearch) in 2009 as part of their new series. They consist of an environment that runs in real-time, shifting slowly from periods of brightness to darkness. Continuing to explore extended time frames but also pursue stillness and a gradual shifting state.

The different groups of flying machines called Whirligigs have a biological and mechanical appearance. Occasionally, they call out their unique song, seeming restless in their abandoned world. When darkness falls the Whirligigs pulsing lights and glowing smoke calls are electrified. Each Whirligig group has a certain lifespan and when this ends a new generation is created, with unique calls, propellers and nose cones patterns. They all have an energy level and when this drops they try and perch on a wire to rest and recharge, slipping gradually into hibernation.

This artwork uses a new compositing tool developed by boredomresearch to allow for the live compositing of animations. The animations rely on artificial intelligence to move the characters they include and do not require interaction. boredomresearch often think of themselves as employing computer gaming technology to create landscape paintings and life studies that move. Many of their works have been created using modelling techniques similar to those used by scientists to study naturally occurring phenomena. However their aim is to create something new of intrigue and beauty.

This artwork was produced using Processing and Blender 3D.


Many countries in sub-Saharan Africa have liberalized markets to improve efficiency and enhance market linkages for
smallholder farmers. The expected positive response by the private sector in areas with limited market infrastructure
has however been disappointing. The functioning of markets is constrained by high transaction costs and coordination
problems along the production-to-consumption value chain. New kinds of institutional arrangements are needed to
reduce these costs and fill the vacuum left when governments withdrew from markets in the era of structural adjustments.
One of these institutional innovations has been the strengthening of producer organizations and formation of collective
marketing groups as instruments to remedy pervasive market failures in rural economies. The analysis presented here
with a case study from eastern Kenya has shown that while collective action – embodied in Producer Marketing
Groups (PMGs) – is feasible and useful, external shocks and structural constraints that limit the volume of trade and
access to capital and information require investments in complementary institutions and coordination mechanisms to
exploit scale economies. The effectiveness of PMGs was determined by the level of collective action in the form of
increased participatory decision making, member contributions and initial start-up capital. Failure to pay on delivery,
resulting from lack of capital credit, is a major constraint that stifles PMG competitiveness relative to other buyers.
These findings call for interventions that improve governance and participation; mechanisms for improving access to
operating capital; and effective strategies for risk management and enhancing the business skills of the PMGs.


Draft genome sequences have been determined for the soybean pathogen Phytophthora sojae and the sudden oak death pathogen Phytophthora ramorum. Oömycetes such as these Phytophthora species share the kingdom Stramenopila with photosynthetic algae such as diatoms, and the presence of many Phytophthora genes of probable phototroph origin supports a photosynthetic ancestry for the stramenopiles. Comparison of the two species' genomes reveals a rapid expansion and diversification of many protein families associated with plant infection such as hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in particular, a superfamily of 700 proteins with similarity to known oömycete avirulence genes.


Switzerland is renowned for having a diverse linguistic and dialectal landscape in a comparatively small and confined space. Possibly, this is one of the reasons why Swiss German dialects have been investigated thoroughly on various linguistic levels. Nevertheless, natural speech intonation has, until today, not been examined systematically. The aim of this study is to analyze natural Swiss German fundamental frequency behavior according to linguistic, paralinguistic, and extralinguistic variables, using statistical tests against the backdrop of detecting dialect-specific patterns as well as cross-dialectal differences. The intonation analyses were conducted with the mathematically-formulated Command-Response model. This is the first large-scale study that applies this framework on a large corpus of natural, dialectal speech. This contribution provides a holistic account of the truly multilayered features of natural speech intonation and brings to light detailed underlying patterns of Swiss German dialectal fundamental frequency behavior. The book is mainly targeted at linguists, speech scientists, as well as dialectologists.


The 4th workshop within the IIASA project "Challenges and Opportunities of Economic Integration within a Wider European and Eurasian Space" held on 12-13 May, 2015 in Laxenburg, Austria delivered the latest insights into the risks, uncertainties, trends and opportunities around energy trade and energy security of the EU, EAEU and neighboring countries. The discussions focused mostly on natural gas covering conventional, LNG and shale gas, on nuclear energy, as well as on the potential for a common electricity market between some EU, EAEU and neighboring countries.

To foster interdisciplinary and international dialogue on the topic, the workshop invited distinguished academics and policymakers from around the world, including Tair Mansurov, Member of the Board – Minister in charge of Energy and Infrastructure, Eurasian Economic Commission; Peter Balas, Deputy Director General, DG Trade, European Commission and Head, Support Group for Ukraine; Jean-Arnold Vinois, European Commission Directorate General for Energy; Pavel Kabat, Director General and Chief Executive Officer, IIASA; Evgeny Vinokurov, Director, Centre for Integration Studies, Eurasian Development Bank; among many others, with a total of 48 participants.

The participants had impassionate exchanges over sometimes rather different views, yet they were able to concur on a number of points. This demonstrates the value of IIASA as a platform for open exchange of views between European and Eurasian experts and policymakers on currently controversial issues in the context of Euro-Eurasian economic integration.

Selected Seminar Highlights:

During the course of the seminar, the experts brought forward the following proposals:

• Creation of a common EU - EAEU electricity market could be useful, since it could stimulate large-scale construction of various types of generation assets in the Kaliningrad Region and in Belarus (nuclear, hydro and thermal power stations), that could provide power to Poland, Lithuania and other neighboring countries.
• Euro-Eurasian energy cooperation could be enhanced on the basis of the Energy Charter Treaty (1998) mechanism (although in case of Russia only if it decides to revise its earlier decision to leave the Treaty).
• Development by the Eurasian Economic Commission of a common Emissions Trading System (ETS) in line with EU norms can help increase compatibility in the future thus enhancing prospects of a common EU - EAEU emission inventory market.
• Joint development of the Arctic shelf can be a promising and prestigious long-term project of economic and investment cooperation between the EU and Russia.
• Commitment towards the work of the EU - Russia Gas Advisory Council and the "EU-Russia Gas Cooperation Roadmap till 2050" could be increased by both – Russia and the EU member states.
• An international gas research cooperation program between the European Commission and research institutes of different regional players (not only Russia) could be established which might help gaining objectivity and transparency on forecasts in the gas market.
• The repeated gas supply crises between Russia and the EU over supply to and transit via Ukraine make the efforts on maintaining cooperation and dialogue between the two even more important.
• Despite the fact that Ukraine intends to integrate its energy system into the European Network of Transmission System Operators for Electricity (ENTSO-E), maintaining interconnections with the Russian and Belarusian electricity grid can help them decrease electricity price inflation during the transition period.
• Energy efficiency in the Ukrainian household sector is a topic of joint interests and needs. Participants of the seminar proposed cooperation between the Eurasian Economic Commission and the respective Ukrainian research institutions for comparing approaches being adopted both in Ukraine and by the member states of the Eurasian Economic Union.
• IIASA's role as a platform for discussing energy matters between the EU and Russia/EAEU as equals can be crucial.

Seminar Focus Areas:

During the workshop the participants came to distinguish six game changers that currently affect Euro-Eurasian energy relations and policies.

1. Gas supply diversification of the European market and the rise of shale and LNG
2. Two cornerstones of the EU energy policy – anti-monopoly and supra-national regulations
3. Prospects and implications of energy efficiency improvements and climate change targets across the region
4. Local and regional effects of the Ukrainian crisis onto Euro-Eurasian energy relations and policies
5. Perspectives of the new energy deals between China and Russia
6. Perspectives of EU - EAEU energy market integration


A review of fatigue data and reassessment of the 1983 fatigue specification resistance functions has been conducted. Since the AASHTO specification fatigue resistance provisions were introduced in 1974, several major studies have been conducted around the world. By reviewing the results of these studies on large-scale welded steel test specimens, the original database has been broadened to include a wider range of detail type and sizes. A revised set of fatigue design curves were proposed and adopted by AASHTO in 1986 that better estimates the fatigue resistance of welded steel details. Though similar to the 1983 AASHTO curves, the new curves are more uniform and parallel; each curve is set at a constant slope of minus 3. 0. The AASHTO Connection Descriptions and Conditions have been revised and expanded to better represent the increased database.


Purpose: The aim of this paper is to describe service users' perspectives on the difference between high secure long-stay forensic psychiatric services in the Netherlands and high secure forensic psychiatric care in England. These perspectives are relevant in considering the benefits of a similar long-stay service in England.
Method: A current in-patient detained in a high secure hospital in England and other mental health service users and carers with experience in forensic-psychiatric settings were asked to watch a documentary on a Dutch high secure long-stay service. Then they were invited to make comparisons between this service and high-secure care in England. These perspectives were gained in the context of their membership of the Service User Reference Group of an externally funded study on long-stay in forensic-psychiatric settings in England.
Findings: Our small group of participants highlighted the importance of relational security, meaningful occupation, autonomy, positive therapeutic relationships with staff and a homely environment for those with lengthy admissions and perceived these to be better met in the Dutch service. These factors might contribute to improved quality of life that services should strive to achieve, especially for those with prolonged admissions.
Practical Implications: Perspectives of service users with lived experience of long-stay in forensic settings are important in informing service developments. Lessons can be learnt from initiatives to improve the quality of life of long-stay services in other countries and consideration be given on how to best manage this unique group.
Originality/Value: To our knowledge this is the first study asking service users about their view on forensic services in other countries. Our findings suggest that service users have valuable contributions to make to aid service developments and should be involved in similar such exercises in the future.


The machining of small holes and array holes has been a difficult problem in machining field. Tiny hole is widely used in mechanical field, for instance, fuel injection nozzles, spinneret holes for synthetic fibers and wire drawing dies. This paper investigated the application of EDM (electrical discharge machining) to the fabrication of micro structures. There are obvious limitations in the process of micro-electrical discharge machining, such as electrode wear, unstable discharge condition and low machining efficiency. The effects of EDM parameters were investigated, such as voltage, pulse frequency, and frequency of ultrasonic vibration applied to electrode. Micro holes were machined with Pt electrode made by focused-ion-beam chemical vapor deposition (FIB-CVD) and Cu electrode made by wire-electrode cutting. The comparison experiments between EDM and ECM (electrochemical machining) indicated that the processing of ECM has serious stray current corrosion and poor machining precision. Moreover, the workpiece vibration was firstly proposed to be utilized in the micro-electrical discharge machining. It can be concluded that maximum machine could be obtained under the amplitude ratio of 76%, which was an appropriate parameter.


This paper examines the readability of sustainability reporting in the annual reports, and stand-alone reports of New Zealand listed companies over a ten-year period. Sustainability reporting was manually extracted from 264 reports, and readability software was used to identify the readability scores using five readability indices. Additionally, the effects of reporting quantity, environmental sensitivity, and global listing on the readability of sustainability reporting were examined. The results show that over the ten-year period readability has improved by only 6.5 per cent, despite a substantial increase in the number of companies reporting sustainability information, and an increase in the quantity of sustainability reporting from almost a third of the companies. This research also finds that there is a statistically significant negative correlation between the average readability score and reporting quantity; meaning longer sustainability reports have lower readability scores (i.e. they are more readable). The findings indicate that environmentally sensitive companies published more readable sustainability information in comparison to companies from non-environmentally sensitive industries. However, in terms of readability, there is no difference between the reports published by companies listed only on the New Zealand Stock Exchange (NZX) and the reports published by companies listed on multiple stock exchanges. This research is the first readability study examining sustainability reporting in New Zealand. It provides companies, users of sustainability information and regulators with knowledge of the readability of voluntary sustainability reporting, showing that little change has occurred over time. It suggests a strong possibility of obfuscation and thus, a risk that sustainability reporting is sending the wrong signal to stakeholders.


Brochure for the Women's History Month celebration, "Women of Courage and Vision," hosted by the Third Infantry Division (Mechanized) at the Hunter Army Airfield serving Fort Stewart in Savannah, Georgia on March 6, 2001. The front cover displays the Third Infantry Division shoulder sleeve insignia, a small crest, and a portrait of Helen W. Snapp surrounded by six smaller images of women in the military, including Rosie the Riveter and women wearing service uniforms. The Sequence of Events listed on the second page includes the names of the speakers for each event: Welcome by Sargent Pandy, National Anthem (stand) by Sargent Requita Williams, Invocation (stand) by Apostle Wilhelmenia Brown, a Video Presentation, Introduction of Speaker by Colonel Betson, Guest Speaker speech by Miss Helen Wyatt Snapp, Unveiling by Third Infantry Soldiers, Presentation by Colonel Betson, Benediction (stand) by Miss Lillian Shun, and finally the Marne Song and the Army Song sung by all. It contains a military biography of Helen Snapp, and the last two pages contain the lyrics for the Marne and Army songs. The back cover displays a crest with the words "Nous Resterons La."


Brian Wilson was the creative genius behind the Beach Boys. He turned a suburban California garage band into a group that took the world by storm with the sound of his songs, including such classics as "Good Vibrations", "California Girls" and "God Only Knows". Brian, Dennis, Carl, Mike and Al were the free-wheeling good-time guys who personified the laid-back, sunny southern California lifestyle. They were the most popular rock group in the world. But the cheerful image belied what was really going on. For the first time, in this long-awaited, no-holds-barred autobiography, Wilson describes his 20 year nightmare of drug addiction, alcoholism, obesity and mental illness. He spent 3 years alone in his room. He lost his family. And he nearly lost his life. Only Brian Wilson can tell the truth behind the rumours and myths about his complex and fascinating life. "Wouldn't It Be Nice" is filled with shocking revelations about his violent father's abuse of him as a child; the bitter infighting among the Beach Boys, which continues to this day; the death of his beloved brother and drug partner Dennis; and the controversies surrounding Dr Eugene Landy, the psychotherapist whom Brian credits with literally saving his life.


Lucifer Yellow CH (LY) is an excellent probe for fluid-phase pinocytosis. It accumulates within the macrophage vacuolar system, is not degraded, and is not toxic at concentrations of 6.0 mg/ml. Its uptake is inhibited at 0 degree C. Thioglycollate-elicited mouse peritoneal macrophages were found to exhibit curvilinear uptake kinetics of LY. Upon addition of LY to the medium, there was a brief period of very rapid cellular accumulation of the dye (1,400 ng of LY/mg protein per h at 1 mg/ml LY). This rate of accumulation most closely approximates the rate of fluid influx by pinocytosis. Within 60 min, the rate of LY accumulation slowed to a steady-state rate of 250 ng/mg protein per h which then continued for up to 18 h. Pulse-chase experiments revealed that the reduced rate of accumulation under steady- state conditions was due to efflux of LY. Only 20% of LY taken into the cells was retained; the remainder was released back into the medium. Efflux has two components, rapid and slow; each can be characterized kinetically as a first-order reaction. The kinetics are similar to those described by Besterman et al. (Besterman, J. M., J. A. Airhart, R. C. Woodworth, and R. B. Low, 1981, J. Cell Biol. 91:716-727) who interpret fluid-phase pinocytosis as involving at least two compartments, one small, rapidly turning over compartment and another apparently larger one which fills and empties slowly. To search for processes that control intracellular fluid traffic, we studied pinocytosis after treatment of macrophages with horseradish peroxidase (HRP) or with the tumor promoter phorbol myristate acetate (PMA). HRP, often used as a marker for fluid-phase pinocytosis, was observed to stimulate the rate of LY accumulation in macrophages. PMA caused an immediate four- to sevenfold increase in the rate of LY accumulation. Both HRP and PMA increased LY accumulation by stimulating influx and reducing the percentage of internalized fluid that is rapidly recycled. A greater proportion of endocytosed fluid passes into the slowly emptying compartment (presumed lysosomes). These experiments demonstrate that because of the considerable efflux by cells, measurement of marker accumulation inaccurately estimates the rate of fluid pinocytosis. Moreover, pinocytic flow of water and solutes through cytoplasm is subject to regulation at points beyond the formation of pinosomes.


We describe an approach to compute filters that automatically performs a spatial frequency selection to improve interclass discrimination and to reduce intraclass sensitivity. This approach is achieved by using as input to the filter synthesis a set of reference images to compute the filters and a set of distorted images to introduce the distortion or noise model of the reference images. Simulation results of correlation examples are provided for two pattern-recognition problems and are compared with the ones obtained with the standard minimum average correlation energy filters.


Faint Lyα emitters become increasingly rarer toward the reionization epoch (z ∼ 6–7). However, observations from a very large (∼5 deg2) Lyα narrow-band survey at z = 6.6 show that this is not the case for the most luminous emitters, capable of ionizing their own local bubbles. Here we present follow-up observations of the two most luminous Lyα candidates in the COSMOS field: "MASOSA" and "CR7." We used X-SHOOTER, SINFONI, and FORS2 on the Very Large Telescope, and DEIMOS on Keck, to confirm both candidates beyond any doubt. We find redshifts of z = 6.541 and z = 6.604 for "MASOSA" and "CR7," respectively. MASOSA has a strong detection in Lyα with a line width of 386 ± 30 km s−1 (FWHM) and with very high EW0 (>200 Å), but undetected in the continuum, implying very low stellar mass and a likely young, metal-poor stellar population. "CR7," with an observed Lyα luminosity of 1043.92±0.05 erg s−1 is the most luminous Lyα emitter ever found at z > 6 and is spatially extended (∼16 kpc). "CR7" reveals a narrow Lyα line with 266 ± 15 km s−1 FWHM, being detected in the near-infrared (NIR) (rest-frame UV; β = −2.3 ± 0.1) and in IRAC/Spitzer. We detect a narrow He ii 1640 Å emission line (6σ, FWHM = 130 ± 30 km s−1) in CR7 which can explain the clear excess seen in the J-band photometry (EW0 ∼ 80 Å). We find no other emission lines from the UV to the NIR in our X-SHOOTER spectra (He ii/O iii] 1663 Å > 3 and He ii/C iii] 1908 Å > 2.5). We conclude that CR7 is best explained by a combination of a PopIII-like population, which dominates the rest-frame UV and the nebular emission, and a more normal stellar population, which presumably dominates the mass. Hubble Space Telescope/WFC3 observations show that the light is indeed spatially separated between a very blue component, coincident with Lyα and He ii emission, and two red components (∼5 kpc away), which dominate the mass. Our findings are consistent with theoretical predictions of a PopIII wave, with PopIII star formation migrating away from the original sites of star formation.


Velo-cardio-facial syndrome/DiGeorge syndrome results from unequal crossing-over events between two 240-kb low-copy repeats termed LCR22 (LCR22-2 and LCR22-4) on Chromosome 22q11.2, comprised of modules, each of which are >99% identical in sequence. To delineate regions in the LCR22s that might contain hotspots for 22q11.2 rearrangements, we scanned the interval for increased rates of recombination with the hypothesis that these regions might be more prone to breakage. We generated an algorithm to detect sites of altered recombination by searching for single nucleotide polymorphic positions in BAC clones from different libraries mapped to LCR22-2 and LCR22-4. This method distinguishes single nucleotide polymorphisms from paralogous sequence variants and complex polymorphic positions. Sites of shared polymorphism are considered potential sites of gene conversion or double cross-over between the two LCR22s. We found an inverse correlation between regions of paralogous sequence variants that are unique to a given position within one LCR22 and clusters of shared polymorphic sites, suggesting that these clusters depict altered recombination and not remnants of ancestral single nucleotide polymorphisms. We postulate that most shared polymorphic sites are products of past transfers of DNA information between the LCR22s, suggesting that frequent traffic of genetic material may induce genomic instability in the two LCR22s. We also found that gaps up to 1.5 kb long can be transferred between LCR22s.


B96 Introduction In the US, prognosis for oral cancer is poor with low 5- and 10-year survival rates. These rates have remained relatively constant over the last three decades, with 20%-30% of oral cancer survivors experiencing a recurrence within two years. Since current treatments are relatively ineffective at inhibiting recurrence, it is important that novel preventive strategies be developed. The hamster cheek pouch (HCP) model has shown that biochemical, molecular and histological changes between humans and hamsters are maintained during oral carcinogenesis. We have used the HCP to demonstrate the chemopreventive efficacy of black raspberries and translated these findings into human clinical trials. We have now focused our efforts on another food-based chemopreventive agent, strawberries, and have recently demonstrated that dietary lyophilized strawberries (LS) significantly inhibited tumor formation in Complete Chemoprevention (CC) and Post-initiation (PI) assays in the HCP model. Epidemiologic and chemoprevention studies have demonstrated that selenium (Se) can decrease the risk and incidence of some human cancers through pathways such as apoptosis, detoxification, and inhibition of proliferation. The current study illustrates ongoing pre-clinical efforts aimed at evaluating the chemopreventive efficacy of selinium (Se)-enriched lyophilized strawberries (LS+Se). Previous studies have shown that elemental and organoselenium compounds inhibited tongue carcinogenesis in animal models. Therefore, we hypothesize that the combinatorial administration of LS+Se will inhibit oral tumorigenesis to a greater extent than LS-alone. Methods Strawberries with bioincorporated selenium (0.5 and 1.0 ppm) were prepared by spraying sodium selenate solution three times on the leaves of the plants just before and during blossom. The HCP model was used to evaluate the ability of LS and LS+Se to inhibit 7,12-dimethylbenz(a)anthracene (DMBA)-induced oral tumors. LS and LS+Se were incorporated into AIN-76A pellets 10% (w/w) and given to hamsters before, during, and after carcinogen treatment (CC). At 12 weeks, lesions in each cheek pouch were enumerated. HCP were excised and stored appropriately for subsequent studies. Results Poisson regression demonstrated that 10% LS and 10% LS+Se [0.5 ppm] significantly inhibited tumor formation by 43% and 59%, respectively, over DMBA-only treated controls. Using logistic regression with the dependent variable being presence or absence of tumors, it was found that LS+Se were 3x as likely to have no tumors (95% CI: 1.31-8.33) as DMBA-only treated HCP. LS-alone was 2.2x as likely to have no tumors, but this difference was not significantly different than DMBA-only treated groups. The presence of leukoplakias was significantly increased with LS+Se and LS, suggesting that progression from premaligant lesions to overt tumors was inhibited by LS and to an even greater effect with LS+Se. Discussion and Conclusion While trends were evident for the combinatorial effects of LS+Se, the current study could not demonstrate statistical significances between the chemopreventive role of LS-alone versus LS+Se. Overall, these experiments provide strong preclinical evidence that the strawberries and strawberries with selenium can prevent or delay the development of oral cavity cancer. Support: NIH/NCI R03CA128043 Citation Information: Cancer Prev Res 2008;1(7 Suppl):B96.


A novel high performance liquid chromatography-mass spectrometry method for simultaneous determination of loganin, morroniside and paeoniflorin in rat plasma was developed, validated and applied to pharmacokinetic study of Liuwei Dihuang pills. Samples were prepared by liquid-liquid extraction with ethyl acetate. Separation was performed on a Wondasil C18 column (150×4.6 mm, 5 μm) using a mixture of methanol and 0.02 % formic acid water solution (28:72, v/v) as the mobile phase. The flow rate and column temperature were set at 0.7 ml/min and 30°. The compounds were detected in selected ion monitoring mode using an ESI source in the negative mode. The method was linear over the ranges of 5-1000 ng/ml for the three analytes, with all determined correlation coefficients exceeding 0.993. All of the lower limits of quantification of the three analytes were 5 ng/ml. The intra-day and inter-day precisions were less than 7.50 %, and the accuracy ranged from –6.57 to 7.90 %. The mean recoveries of the analytes were higher than 68.86 %, and the matrix effects were between 92.35 and 103.54 %. This method was simple, sensitive and reliable, and could be used to monitor pharmacokinetics of loganin, morroniside and paeoniflorin. Moreover, this study might be helpful for quality control and guiding the clinical application of Liuwei Dihuang pills.


Stated preference analyses commonly impose strong and unrealistic assumptions in response to spatial welfare heterogeneity. These include spatial homogeneity or continuous distance decay. Despite their ubiquity in the valuation literature, global assumptions such as these have been increasingly abandoned by non-economics disciplines in favor of approaches that allow for spatial patchiness. This paper develops parallel methods to evaluate local patchiness and hot spots in stated preference welfare estimates, characterizing relevant patterns overlooked by traditional approaches. The analysis draws from a choice experiment addressing river restoration. Results demonstrate shortcomings in standard treatments of spatial heterogeneity and insights available through alternative methods.


Urinary incontinence (UI) and fecal incontinence (FI) are embarrassing and debilitating conditions that are becoming collectively a major, growing health concern for men and women of all ages worldwide. Recent research showed that professional care-givers in long-term facilities (nursing homes) were not confident in their skills to care for FI residents. This long-term care residential-based study conducted in Ontario Canada was purposed to identify gaps in the knowledge of professional care-givers. Based upon the results of this study there appeared to be room for improvement in the management of both UI and FI in long-term care residences in Ontario. It is recommended that a first tranche of participatory education include topics such as: the causes of FI; the value of using assessments, histories and diaries in moving from treatment to management; dealing with residents that are incontinent as well as depressed.


A statistical analysis of the effects of film nonlinearities on wavefront-reconstruction images of diffuse objects is presented. Regardless of the particular nature of the nonlinearity, the image distortions are shown to consist of additive irradiance contributions which may be found as multiple autoconvolutions of the ideal image irradiance distribution produced by a linear film. The predictions of the general nature of the image distortions are supported by experimental evidence.


Over the past years, the use of epidural anesthesia as an intervention for pain relief has increased in the labor and delivery setting. Exploration of the literature has not identified what effects the addition of this technology has had on the normal childbirth process and those participating in childbirth, specifically the new father. The purpose of this study was to explore first-time fathers' perceptions of their feelings and concerns during the various phases of the labor and delivery experience in which epidural anesthesia is used. The study addresses the following research questions: (a) What are the perceptions of first-time fathers regarding their feelings and concerns at each of the following three stages in the labor and delivery experience: pre-epidural, post-epidural, and at time of delivery of their newborn?; and b) Do the levels of concerns and feelings differ during the various stages identified previously? The convenience sample consisted of first-time fathers whose newborns were delivered in a small Midwest, community hospital. Subjects met the following criteria: a) married at least one year; (b) first baby for both father and mother; (c) attendance at childbirth education classes; and (d) use of epidural anesthesia on spouse during childbirth. Fathers were surveyed through a self-administered questionnaire which was partly derived from The Berry Expectant Fathers Stress Index (BEFSI). Prior to administration, the questionnaire was reviewed by a panel of expert nurses for content and readability. The data from the questionnaires regarding perception and relevant demographic data were analyzed using the Statistical Package for the Social Sciences (SPSS/PC+). The results of the study found that fathers had five feelings and four concerns during childbirth. Feelings included: anxiousness, fear, happiness, confidence and closeness. Concerns included: concern for spouse, concern for baby, concern for self, and concern for the progress of labor. These feelings and concerns were reported at different levels during childbirth.


. With the recent advent of the ability to separate coal into maceral concentrates of high purity, the individual constituents of coal can now be analyzed separately, without their mutual interference, giving a much better understanding of the macromolecular structure of coal. The sporinites from two Pennsylvanian age coal samples (Illinois Basin, U.S.A.) were studied, one from a vitrinite-rich high-volatile bituminous coal, the other from a liptinite-rich high-volatile bituminous coal of slightly higher rank. Sporinites were isolated from each coal by density gradient centrifugation. The sporinite of the vitrinite-rich coal was compared chemically and petrographically with the parent coal and with the sporinite of the liptinite-rich coal. The fluorescence spectrum of the sporinite from the liptinite-rich coal is shifted to the red end of the spectrum, which may be accounted for by the somewhat higher rank of the sample and/or by differences in the original assemblage of spores. The lack of chemical differences between the extracts of the sporinite and its whole coal reinforce the concept of bitumen as an homogeneous mobile phase pervading the coal. Thus, extract chemistry seems an unsuitable technique for distinguishing between macerals from the same coal. Hopane and sterane distributions in the sporinite and parent coal pyrolyzates are very similar, but the two materials can be readily distinguished by the distribution of tetracyclic diterpanes of the phyllocladane type, which are biological marker compounds derived from higher plant material. Overall, the sporinite is considerably more paraffinic in character and has a greater preponderance of straight-chain alkane moieties than the coal as a whole. In the case of the vitrinite-rich coal, the whole-coal structure appears significantly more polyaromatic than the sporinite. The distributions of thiophenic compounds differ in the pyrolyzates of the two materials. The sporinite from the liptinite-rich coal is even less polycondensed than the sporinite from the vitrinite-rich sample. The chemical and petrographic differences of the two sporinites probably reflect the different assemblages of spores in the original peats and their different diagenetic histories.


The kinetics of the droplet formation during the spinodal decomposition (SD) of the homopolymer blends has been studied by numerical integration of the Cahn-Hillard-Cook equation. We have found that the droplet formation and growth occurs when the minority phase volume fraction, f m , approaches the percolation threshold value, f thr = 0.3 ± 0.01. The time for the formation of the disperse droplet morphology (coarsening time) depends only on the equilibrium minority phase volume fraction, f m , f m , approaches its equilibrium value lorarithmically at the late SD stages, and, therefore, the coarsening time decreases exponentially as the average volume fraction or the quench depth decrease. Since the temporal evolution of the total interfacial area does not depend the quench conditions and blend morphology, the average droplet size and the droplet number density is determining by the coarsening time. Within the time scale studied, the droplet number density decreases with thime at t -0.63±0.03 ; the average mean curvature decreases at t -0.35±0.05 ; the average Gaussian curvature decreases as t -0.42±0.03 , and the average droplet compactness (∼v/s 3/2 where S is the surface area and V is the volume) approaches a spherical limit logarithmically with time. The droplets with larger area have lower compactness and in the low compactness limit their area is a parabolic function of compactness. The size and shape distribution functions have been also investigated.


Since the mid-1990s, scholars from different traditions have challenged standard assumptions about the nature of contemporary civil wars. On the one hand, they argue, armed organisations and combatants increasingly take part in criminal activities and behave as thugs rather than soldiers. Civilian collaboration, on the other hand, is less based in collective political action and more on individualism and opportunism. New findings from the Crisis States Research Centre challenge these claims based on the study of an episode of armed conflict and political mobilisation in a Colombian region during the late 1990s and early 2000s.This paper raises questions surrounding the perceived divide between organised crime and politics. It shows how the involvement of criminals in armed organisations and of the latter in criminal activities does not preclude their participation in local political processes or strip their activity of their intrinsic political nature. Furthermore, it shows that the behaviour of civilians vis-a-vis armed organisations is not necessarily disparate or opportunistic. Rather, this research indicates that complex 'alliances' and co-operation exist between armed organisations and civilians and will evolve in relation to challenges and opportunities presented by public policy-making and changing patterns on territorial control. Conclusions drawn from this paper suggest that the political dimensions of the Columbian conflict should not be underestimated as they may provide valuable insight into this and other instances of 'irregular war'.


Analyses of genetic data observed on groups of related individuals frequently require the computation of probabilities on pedigrees. Existing methods are computationally intensive and can be infeasible on large and complex pedigrees. The estimation of genotypic configurations on pedigrees from phenotypic data, whether for prior studies of the likely power of potential data to decide between alternative genetic hypotheses, as an implicit stage in fitting a genetic model, or as an end result in a genetic counselling context, is one component of such analyses. An alternative approach to this reconstruction problem can be based on procedures used in Imaging Analysis, all closely related to the method of Metropolis. These procedures exploit the local nature of the information in a pedigree thus permitting the definition of a neighbourhood system whereby, conditional on the neighbours, the genotypes of individuals are independent.
The ICM procedure iteratively updates the genotype estimate of each individual in turn, replacing the current estimate by the mode of the local conditional posterior distribution. Increase and convergence of the overall posterior probability of genotypes given phenotypes is assured, but the restoration does not necessarily converge to a global maximum of the posterior distribution. Alternatively, one can update a vector of single-individual genotype probabilities rather than the discrete genotype, again conditionally on current neighbouring values. Another possibility is to update each individual's genotype estimate by sampling from the local conditional posterior distribution. This method is known as the Gibbs sampler. Multiple realisations of the Gibbs sampler can provide estimates of the true posterior distribution of genotypes given phenotypes on the pedigree, and, when used in conjunction with simulated annealing can find the global maximum of this distribution.
These approaches to genotypic restoration are modified and tested by application to a very complicated pedigree of Greenland Eskimos. The areas of Pedigree Analysis to which such approaches are most directly relevant include genetic counselling and selective animal breeding together with questions about ancestral genotypes and the ancestral paths of rare alleles.


Operating Outside of Empire: Trading Citizenship in the Atlantic World, 1783-1815, looks at markets and ships as spaces for negotiation between merchants and the state. The dissertation follows the experiences of former British colonists in America who won independence and then immediately tried to find a way to get back into the British empire. For American merchants, such as Nicholas Low, William Constable, and Thomas Handasyd Perkins, the inconsistently-governed Caribbean provided an entry point to the greater British Atlantic and the markets of the empire. These merchants won access by exploiting the opportunities offered by environmental catastrophes, slave rebellions and trade wars. The dissertation approaches the trade in identity through five chapters that trace the connections formed between transatlantic merchants and their relationship to an increasingly intrusive and powerful state apparatus. By taking citizenship and belonging in a new direction, the dissertation looks at the ways in which commerce reshaped nationality and challenged what it meant to be a citizen in the Atlantic World. Before the idea of the nation was fully formed, merchants, statesmen, and philosophers offered an alternative conception of belonging and nationality that was much more fluid and malleable. By focusing on information as a valuable commodity, the dissertation shows how letters filled with rumors and gossip sustained an economy without the official support of a government monopoly and even in opposition to the Royal Navy. It was through their discussions of demand and opportunity that merchants participated in debates about the nature of commerce, the loyalty of the citizen, and the role of the state in regulating national identity and international trade. Operating Outside of Empire: Trading Citizenship in the Atlantic World, 1783-1815


Neuronal stretching during concussion alters glucose transport and reduces neuronal viability, also affecting other cells in the brain and the Blood Brain Barrier (BBB). Our hypothesis is that oxidative stress (OS) generated in neurons during concussions contributes to this outcome. To validate this, we investigated: (1) whether OS independently causes alterations in brain and BBB cells, namely human neuron-like, neuroblastoma cells (NCs), astrocyte cells (ACs) and brain microvascular endothelial cells (ECs), and (2) whether OS originated in NCs (as in concussion) is responsible for causing the subsequent alterations observed in ACs and ECs. We used H2O2 treatment to mimic OS, validated by examining the resulting reactive oxygen species, and evaluated alterations in cell morphology, expression and localization of the glucose transporter GLUT1, and the overall cell viability. Our results showed that OS, either directly affecting each cell type or originally affecting NCs, caused changes in several morphological parameters (surface area, Feret diameter, circularity, inter-cellular distance), slightly varied GLUT1 expression and lowered the overall cell viability of all NCs, ACs, and ECs. Therefore, we can conclude that oxidative stress, which is known to be generated during concussion, caused alterations in NCs, ACs, and ECs whether independently originated in each cell or when originated in the NCs and could further propagate the ACs and ECs. CONCUSSION: EXAMINING THE EFFECT OF NEURONAL OXIDATIVE STRESS ON THE PATHOPHYSIOLOGY OF BRAIN AND BLOOD BRAIN BARRIER CELLS


We develop a new technique for verifying temporal properties of infinite-state (distributed) systems. The main idea is to reduce the temporal verification problem to the problem of verifying the safety of infinite-state systems expressed in first-order logic. This allows to leverage existing techniques for safety verification to verify temporal properties of interesting distributed protocols, including some that have not been mechanically verified before. We model infinite-state systems using first-order logic, and use first-order temporal logic (FO-LTL) to specify temporal properties. This general formalism allows to naturally model distributed systems, while supporting both unbounded-parallelism (where the system is allowed to dynamically create processes), and infinite-state per process. The traditional approach for verifying temporal properties of infinite-state systems employs well-founded relations (e.g. using linear arithmetic ranking functions). In contrast, our approach is based the idea of fair cycle detection. In finite-state systems, temporal verification can always be reduced to fair cycle detection (a system contains a fair cycle if it revisits a state after satisfying all fairness constraints). However, with both infinitely many states and infinitely many fairness constraints, a straightforward reduction to fair cycle detection is unsound. To regain soundness, we augment the infinite-state transition system by a dynamically computed finite set, that exploits the locality of transitions. This set lets us define a form of fair cycle detection that is sound in the presence of both infinitely many states, and infinitely many fairness constraints. Our approach allows a new style of temporal verification that does not explicitly involve ranking functions. This fits well with pure first-order verification which does not explicitly reason about numerical values. In particular, it can be used with effectively propositional first-order logic (EPR), in which case checking verification conditions is decidable. We applied our technique to verify temporal properties of several interesting protocols. To the best of our knowledge, we have obtained the first mechanized liveness proof for both TLB Shootdown, and Stoppable Paxos.


Humans represent and discriminate the objects in the same category using their properties, and an intelligent robot should be able to do the same. In this paper, we build a robot system that can autonomously perceive the object properties through touch. We work on the common object category of clothing. The robot moves under the guidance of an external Kinect sensor, and squeezes the clothes with a GelSight tactile sensor, then it recognizes the 11 properties of the clothing according to the tactile data. Those properties include the physical properties, like thickness, fuzziness, softness and durability, and semantic properties, like wearing season and preferred washing methods. We collect a dataset of 153 varied pieces of clothes, and conduct 6616 robot exploring iterations on them. To extract the useful information from the high-dimensional sensory output, we applied Convolutional Neural Networks (CNN) on the tactile data for recognizing the clothing properties, and on the Kinect depth images for selecting exploration locations. Experiments show that using the trained neural networks, the robot can autonomously explore the unknown clothes and learn their properties. This work proposes a new framework for active tactile perception system with vision-touch system, and has potential to enable robots to help humans with varied clothing related housework.


Aligning protein-protein interaction networks from different species is a useful mechanism for figuring out orthologous proteins, predicting/verifying protein unknown functions or constructing evolutionary relationships. The network alignment problem is proved to be NP-hard, requiring exponential-time algorithms, which is not feasible for the fast growth of biological data. In this paper, we present a novel protein-protein interaction global network alignment algorithm, which is enhanced with an extended large neighborhood search heuristics. Evaluated on benchmark datasets of yeast, fly, human and worm, the proposed algorithm outperforms state-of-the-art. Furthermore, the complexity of ours is polynomial, thus being scalable to large biological networks in practice.
Keywords
Heuristic, Protein-protein interaction networks, network alignment, neighborhood search
References
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We report the results of searches for B+→J/ψη′K+ and B0→J/ψη′KS0 decays, using a sample of 388×106 BB pairs collected with the Belle detector at the Υ(4S) resonance. No statistically significant signal is found for either of the two decay modes and upper limits for the branching fractions are determined to be B(B+→J/ψη′K+)<8.8×10-5 and B(B0→J/ ψη′KS0)<2.5×10-5 at 90% confidence level. © 2007 The American Physical Society.


Glycoside hydrolases (GHs) are enzymes that are able to rearrange the plant cell wall polysaccharides, being developmentaland stress-regulated. Such proteins are used in enzymatic cocktails for biomass hydrolysis in the second-generation ethanol (E2G) production. In this chapter, we investigate GHs identified in plant cell wall proteomes by predicting their functions through alignment with homologous plant and microorganism sequences and identification of functional domains. Up to now, 49 cell wall GHs were identified in sugarcane and 114 in Brachypodium distachyon. We could point at candidate proteins that could be targeted to lower biomass recalcitrance. We more specifically addressed several GHs with predicted cellulase, hemicellulase, and pectinase activities, such as β-xylosidase, α and β-galactosidase, α-N-arabinofuranosidases, and glucan β-glucosidases. These enzymes are among the most used in enzymatic cocktails to deconstruct plant cell walls. As an example, the fungi arabinofuranosidases belonging to the GH51 family, which were also identified in sugarcane and B. distachyon, have already been associated to the degradation of hemicellulosic and pectic polysaccharides, through a peculiar mechanism, probably more efficient than other GH families. Future research will benefit from the information available here to design plant varieties with self-disassembly capacity, making the E2G more cost-effective through the use of more efficient enzymes.


With the
implementation of the Official Mexican Standard NOM-011-CONAGUA-2000 [1], the
water balance of 730 basins has been calculated and its water availability
agreement is published. This rule points out to allocate water for the
environment only as an annual volume since methods for estimating environmental
flows were not standardized in the country. For this reason, The Water Agency
(CONAGUA) issued the standard NMX-AA-159-SCFI-2012 [2], to assess environmental
flows needed both, at the strategic level in Integrated Water Resources
Management (IWRM), or as part of the Environmental Impact Assessment (EIA) of
large hydraulic projects. For over ten years, this standard was developed and
finally published in September 2012 [3]. It explains different methods from
hydrological to holistic approaches, with examples for the country. Its
application will cover the urgent need to preserve water for ecosystems in
watersheds with high ecological importance and low stress for water use. In
this paper, an analysis of the environmental flow standard and examples of the
suggested hydrological methods are presented. For its implementation, some
steps are taking place, mainly establishing environmental water reserves and
building capacities. In addition, environmental allocations are becoming a
common practice for all water projects, as well as setting limits to
hydrological alterations by hydroelectric dams. The standard promotes the use
of technical integration tools to analyze the responses of ecosystems to
changes in the flow regime and adaptive management under different scenarios of
water use. Although the main steps have been taken, its implementation as mandatory
rule will take time.