Full Backing Research Articles

Non-coding RNA bioinformatics platform for full backing of the high-throughput sequencing experiments generated by next-generation sequencing technologies

Motivations. Short non-coding RNA molecules (20-30 nucleotides long) play an important role in the regulation of gene expression by interacting with their target RNAs. This interaction generally downregulates gene expression either affecting RNA stability or repressing translation. Different classes of small regulatory non coding RNAs (sncRNAs) have been discovered and studied so far, and new families continue to be described, which differ in the proteins required for their biogenesis, the mechanism of target recognition and regulation, and the biological pathways they control [1,2]. In particular, three major classes of sncRNAs have been mostly investigated: small interfering RNAs (siRNAs), micro-RNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) [1,2,3]. siRNAs direct the endonucleolytic cleavage of their target RNAs through a mechanism known as RNA interference (RNAi), miRNAs can repress translation or direct degradation of their target mRNA generally through imperfect complementary pairing on their 3'UTRs, whereas the major role of piRNAs is to ensure germline stability by repressing transposable elements (TEs). Recently, the advent of new Next-Generation Sequencing (NGS) technologies has awfully increased the throughput of transcriptome studies, thus allowing an unprecedented investigation of non-coding RNAs. Regulatory pathways involving ncRNAs, such as miRNAs, are now being elucidated in detail and functions for long non-coding RNAs are also emerging. The huge amount of transcript data produced by high-throughput sequencing requires the development and implementation of suitable bioinformatics workflows for their analysis and interpretation. Here we describe here a bioinformatics resource to classify and analyze the non-coding RNA component of human transcriptome sequence data obtained by different NGS platforms (Roche 454, Illumina and Solid). Methods. The ncRNAs bioinformatics platform is organized according to a typical three tier architecture: an analysis tier for ncRNAs detection, classification and functional analyses; a data tier made up of a data-warehouse used to store the analysis results, the ncRNAs reference database (a non-redundant collection of ncRNAs sequence retrieved from fRNAdb, RNAdb, mirBASE, NONCODE and others), the reference genome and other useful annotation database like HGNC nomenclature [4], Sequence Ontology (SO) [5] and Entrez Gene; a web tier module for querying the analysis results and the annotation stored in the ncRNAs reference database. The core of the platform is the analysis workflow. In figure 1 we show the pipeline for classification and functional annotations of non-coding RNAs (ncRNAs) fraction obtained through high-throughput sequencing (HTS) experiments using different NGS technologies. The input data for the bioinformatics platform can be either the reads data obtained by different NGS platforms (Roche 454, Illumina and Solid) or previously mapped reads stored in users' SAM/BAM files. Results. The ncRNA bioinformatics platform - through a combination of an analyses pipeline, a datawarehouse and a user-friendly web interface - is able to: i. detect and classify reads in known functional ncRNA categories using Sequence Ontology classification, HGNC nomenclature, gene names and miRNA accessions; ii. extract reads collections belonging to a givencategory for further analysis; iii. quantify ncRNA expression based on annotations derived from different reference ncRNA databases; iv. generate some statistics of expressed ncRNAs, indicating the RPKM (reads per kilobase of RNA model per million mapped reads)value for each Sequence Ontology class; v. detect differential expression of ncRNAs between two conditions (i.e. normal/pathological); vi. create a collections of interesting clusters of reads mapped on the genome but not detected as known ncRNA; vii. filter out reads mapping to ribosomal RNAs and mtDNA transcripts; viii. create a collection of unmapped residual reads (chimeras, artifacts, and contaminations).

Central Banks Quasi-Fiscal Policies and Inflation

Although central banks have recently taken unconventional policy actions to try to shore up macroeconomic and financial stability, little theory is available to assess the consequences of such measures. This paper offers a theoretical model with which such policies can be analyzed. In particular, the paper shows that in the absence of the fiscal authorities' full backing of the central bank's balance sheet, strange things can happen. For instance, an exit from quantitative easing could be inflationary and central banks cannot successfully unwind inflated balance sheets. Therefore, the fiscal authorities' full backing of the monetary authorities' quasi-fiscal operations is a pre-condition for effective monetary policy.

Editorial: Onwards and Upwards-The Future Is Bright for Chemistry!

Editorial: Onwards and Upwards-The Future Is Bright for Chemistry!

Coming soon: nowhere to hide for hospital managers

Hospital and health care managers and administrators will in future be measured against mandatory core standards and judged on outcomes, with little place to hide and less room to shift responsibility, the country’s new standards certification chief warned last month. Dr Carol Marshal, Director of the Office of Healthcare Standards Compliance (OHSC), in the national Department of Health has the full backing of her Director General, Precious Matsotso. This emerged in a speech the pair co-wrote for a health care safety conference in Cape Town last month. It became clear from the speech, delivered on Matsoso’s behalf by Marshal and in a later interview with Marshal, that the ‘slap on the wrist’ approach – driven by a plethora of patient safety policies/guidelines and the absence of a uniform, credible means of probing health care delivery problems – could soon be history.

Overstepping the Balkan boundaries: The lesser known history of Yugoslavia's early relations with Asian countries (new evidence from Yugoslav/Serbian archives)

New discovery of some previously unknown documents from the major Yugoslav/Serbian archives has brought forward some of the long forgotten facts about Yugoslavia's early engagements with certain Asian countries. The leading event among all these was the clandestine recognition of the Republic of China in June 1947 (with the full backing of the USSR), in the light of which special ties with Chinese, Indian, and some Burmese communists were established.

Pedro de Perea and the Colonization of Sonora

Pedro de Perea and the Colonization of Sonora David Yetman (bio) In 1640 or somewhat earlier the first non-clerical Spaniards settled in Sonora and in so doing stirred up a conflict with Sonoran Indians over land rights that lasted for nearly two decades, from roughly 1640 through 1658.1 Jesuit missionaries advised the Indians to take legal action against the settlers. The document that appears in this article portrays the strategy the Indians and their advisors employed to reclaim lands that Spaniards had taken from them. It also reveals the response of Spanish courts to those strategies. Led by a military captain on a civilian mission, Spanish soldiers and settlers (the two often played the same role) ventured into what is now Sonora, not seeking a military conquest but intent on establishing a colony. Their foray had the full backing of the Crown, and they considered their mission a license to civilize the region, i.e., establish an enclave of Spanish culture, institute European customs and norms to guide the "barbarian" native peoples, and, even more important, extract wealth from the land. If Indians stood in the way of convenient development of human and natural resources, so much the worse for them. In this case, the nondescript Eudeve settlement of Tuape on the Río San Miguel, a minor, ephemeral stream in central Sonora, became the location of a struggle that would be repeated numerous times in northwest New Spain in the following 150 years. It would also symbolize the conflicting currents in Spanish expansionism: evangelizing and pacifying native peoples versus expanding the royal treasury and establishing Spanish colonies in lands claimed by the king. The conflict would set the stage for Sonora's colonization and outsiders' eventual appropriation of Indian lands and Indian water. The clash of forces would continue through the expulsion of the Jesuits in 1767 and on through Mexican independence. It [End Page 33] continues today in the form of the neoliberal drive against cooperatively and communally owned lands in Mexico. In the Tuape case, the facts clearly favored the Indians, as all parties acknowledged, yet the authorities were reluctant to rule in their favor. With evidence presented by a Jesuit who knew the Indians well, supported by the Indians' intimate knowledge of the land and their stubborn persistence and the demonstrable improbability of the Spaniards' land claims, the Spanish courts were forced to recognize the validity of the Indians' petition. Still, the courts, as far as the documentary record demonstrates, did not rule against the settlers. Instead, they brought pressure on the Spaniards involved to relinquish their holdings without issuing a formal ruling against them. Prior to 1640 the only Europeans to be found in Sonora,2 apart from a smattering of prospectors in search of precious metals, were priests—a couple of dozen Jesuits and a small handful of Franciscans. These resided in newly created mission communities, not on landed estates under private ownership. Indeed, the Crown entrusted Jesuits with "pacifying" the natives, converting them to Catholicism, and shaping them into a new breed of peasantry freed from their "savage" past, humbly, quietly, and piously tilling the land and reaping harvests. Native uprisings had frustrated the Crown's earlier attempts at colonization in what would come to be called the Opatería, roughly corresponding with northeastern Sonora. In 1540 Francisco Vásquez de Coronado attempted to found a settlement at Corazones, probably on the Río Sonora. Coronado left forty soldiers in charge when he departed for the north. After suffering profound mistreatment at the hands of Spaniards, the natives, probably Teguimas, revolted and obliterated the colony, killing all but four of its Spanish settlers. After the Corazones debacle, indigenous Sonorans—Teguimas, Eudeves, Nébomes, Pimas, and Seris (as Spaniards came to call them), seem to have resisted settlement by outsiders. Teguimas and Eudeves became so renowned for the deadly accuracy with which they shot volleys of poisoned arrows at intruders (and perhaps each other), that most expeditions left Sonorans to their own devices.3 By early in the seventeenth century a more systematic Spanish campaign of pacification and conversion of Indians had reached Ostimuri, the land of the Yaquis and Mayos that...

Too long in the rain … rural doctors get some relief

A long-awaited support programme for isolated, under-resourced rural doctors will start in the Eastern Cape this year once a 3-year, R19 million donation from the Clinton Foundation is finalised. The initiative has the full backing of the national and Eastern Cape provincial departments of health, and of the Rural Doctors Association of South Africa (RuDASA). The main target group is private doctors doing sessions in small rural hospitals and clinics, but doctors and pharmacists working full time in these facilities will also benefit. The money will fund ‘practice managers’ or ‘facilitators’, initially in the much neglected Ukhahlamba and Chris Hani districts. If the programme works well it will be extended in 2011 and 2012 to all the rural areas of the Eastern Cape, and the provincial government will start to pick up a portion of the costs. The practice managers will organise much-needed Continuing Professional Development (CPD) sessions within the district at times that private GPs can attend and that are relevant to practice in remote and under-resourced areas. The practice managers will also trouble-shoot (e.g. help to resolve maddening issues such as non-payment of claims/allowances and repair of minor equipment), arrange locums and, if possible, facilitate on-site mentoring by (mostly) retired senior doctors.

EBCOG and the Nordic countries

EBCOG and the Nordic countries

Right of exemption refused

The first application for exemption from the Early Learning Goals made by a childminder has been refused by the DCSF despite the applicant having the full backing of parents, writes Richard House.

New Insights into Rights Offerings as Signals of Firm Quality: Evidence from Australia*

Australian companies can choose among three different types of rights offerings: full standby (also known as “fully underwritten”); uninsured (or “non‐underwritten”); and partial standby (“partly underwritten”). At the same time, each of these three kinds of rights offerings can be either renounceable or non‐renounceable, with the former providing securities that can be sold while in the latter case the rights are forfeited if not exercised.The main argument of this paper is that managers effectively signal the quality of their company through their choice of rights issue method. Consistent with this argument, the authors summarize the findings of their own research showing that high‐quality companies tend to choose full standby rights issues, with the full backing of an underwriter playing a “certifying” role for investors. By contrast, low‐quality firms tend to use partial standby issues with large subscription price discounts, while companies of intermediate‐quality choose uninsured rights issues. The authors also provide evidence that full standby rights issues are positively correlated with expected shareholder takeup, while both partial standby and uninsured issues have a negative correlation with takeup. Consistent with the above findings, the market response is most positive (or least negative) in the case of non‐renounceable, full standby rights issues with relatively low price discounts. The market reaction is most negative for non‐renounceable, partial standby issues with high price discounts.

CPORT: Effective partnership working to optimize chemotherapy capacity in the UK

e20687 Background: Capacity planning in a complex environment such as a chemotherapy unit is a difficult task; combined with ever increasing patient numbers and limited budgets, time and ability to plan is scarce. This project demonstrates how partnership working between the pharmaceutical industry and NHS service providers can optimise chemotherapy capacity in UK centres. Methods: CPORT stands for “Chemotherapy-Planning Oncology Resource Tool”. The tool is a simulator allowing chemotherapy planners to model how different drugregimens, patient flows, resource levels and ways of working influence the performance of a chemotherapy unit in terms of how many patients are treated, how long they wait, and how much care they receive. A small dedicated team at Roche has been working closely with a team of NHS Facilitators, with the full approval and backing of the National Cancer Action Team. The integrated team have been helping with the roll out of the tool, focusing on supporting cancer units implement CPORT from concept through change and sharing best practice. Results: To date more than 2800 simulations have been run through the tool. Service redesign options have been assessed in minutes and hours, as opposed to weeks and months. The simulator has enabled combinations of several service improvement initiatives to be modelled simultaneously, giving managers the ability to model cancer service delivery in a simulated online environment which is both cost free and risk free. Early results include the better coordination of pharmacy and nursing workload to optimise the available capacity; utlising CPORT to plan the merger of two units and model subsequent resource requirements; modelling the relocation of a unit and predicted caseload of patients. Conclusions: This model represents a successful new form of partnership working between the NHS and the industry to increase capacity within chemotherapy services. It promotes equity of service, better access and an improved experience for all patients receiving chemotherapy, embedding and sustaining the concept of capacity planning within the clinical service. No significant financial relationships to disclose.

MCAST – the Malta College of Arts, Science and Technology: a growing facility for vocational training

Against a background of increasingly complex process technology using increasingly complex plant and equipment, the relative lack of vocational courses in the engineering industry gives increasing rise to concern in many parts of the world. MCAST, the Malta College of Arts, Science and Technology, was founded in 2001 with the full backing of the Maltese Government, a clear demonstration of its commitment to the area of vocational education and training. Its founders saw MCAST as having an indispensable role in the development of an inclusive society and as a dynamic engine for the promotion of a knowledge-based economy. Naturally, MCAST was primarily required to provide wide ranging opportunities for all Maltese and Gozitan citizens. The vision was an institution that would be both wanted and respected by industry for its curriculum offering and its responsiveness to industry’s particular needs. At the same time, it was hoped that MCAST would take full advantage of Pan-European collaborative actions and the European exchange programmes for both students and staff. Malta is very well placed geographically to attract students from many other parts of Europe, and especially the Mediterranean shoreline and North Africa, looking for education and training provided using English – a centre of vocational excellence in the region. MCAST has already achieved a great deal and Government support has been sustained and, indeed, increased through investment in physical and human resources. Further, it is a benefi ciary of additional substantial investment through the European Regional Development Fund (ERDF). The European Social Fund (ESF) will sustain a wide range of courses at different levels and emphasise MCAST’s role as a Community College, welcoming: • young students • older workers • returnees to the workforce • adults who wish to upskill, reskill or upgrade their knowledge and competences. The College currently provides for 4500 full-time and 4000 part-time students, through both vocational education and training and academic programmes that prepare students for careers in industry, business or commerce or higher education, in nine ‘institutes’ and the Gozo Centre. The Institute of Mechanical Engineering offers the following courses: • MCAST Foundation Certifi cate in Mechanical Engineering • Diploma in Automotive Maintenance & Repair (CG Prof Grech served as a member of the IFHTSE Executive Committee for several years

Cyprus: Lessons from the debacle of 2004 and the way ahead

It is now a little over a year since the best chance of settling the Cyprus Problem in the 45 years that it has been on the international community's agenda was accepted by two-thirds of the Turkish Cypriots who voted, and rejected by three-quarters of the Greek Cypriots. This sad ending to nearly five years of intensive negotiations under the aegis of the United Nations, with the full backing of the European Union and all the main external powers which have traditionally played a role in Cyprus—Greece, Turkey, Britain and the USA—with the partial exception of Russia, leaves the island, as it has been now for two generations, divided and a bone of contention, causing problems well beyond its own borders.

The Uses of Vietnam in the Age of Terrorism

DURING HIS HISTORIC TRIP TO VIETNAM in November 2000, President Bill Clinton proclaimed the end of an era. Finally, he asserted in a speech to Vietnamese students at Hanoi's National University, America is coming to see as your people have asked for years-as a country, not a war.1 Indeed, the United States had made bold efforts in the preceding few years to move beyond old animosities and to deal with as it dealt with other Asian nations. In 1994, Washington lifted its 19-year-old trade embargo. A year later, the US normalized diplomatic relations with and opened an embassy. During the process, the president and his congressional supporters contended that the time had come at last to embrace the country as a full participant in the globalizing economy. Clinton's trip to capped this period of economic and political, as well as perceptual and semantic, change. Over the years, Vietnam had become an adjective for most Americans, usually affixed to pejorative words like debacle, or syndrome. Clinton's trip, in the words of famed journalist Stanley Karnow, helped exorcize that ghost.2 could once again be just a place on the other side of the world.For a time, it appeared as though Vietnam was indeed losing some of its radioactivity in American politics and culture. In the 1990s, the United States undertook limited military commitments in Bosnia and Kosovo despite the fact that these undertakings violated one of the allegedly iron-clad lessons of Vietnam: if Washington was going to go to war, it must do so with clear objectives, overwhelming force, and full public backing. Perhaps, it seemed, President George H. W. Bush had been right when he declared at the end of the first Gulf war that America's success had kicked the syndrome once and for all.3 In politics, meanwhile, Americans embraced both the draft-evader Bill Clinton and the former POW John McCain. It appeared that the country-or at least much of it-might be letting go of the passions of the era as it entered a new post-Cold War period with new national priorities.In popular culture, too, things seemed to be changing. Hollywood's lone major foray into the War around the turn of the millennium-MeI Gibson's insipid We Were Soldiers Once-departed sharply from earlier movies by trumpeting the manly exploits of American GIs in a context barren of political meaning. The most powerful cautionary tale dealing with American foreign adventures, Black Hawk Down, dealt not with but with the disastrous US intervention in Somalia in 1992 and 1993. Meanwhile, Americans celebrated their victory in the Cold War by rediscovering the greatest generation and the founding fathers, heroes who helped the country feel safely embedded within a long-term pattern of triumph and moral supremacy. Within this resurgent narrative of a victorious and righteous America, seemed increasingly an anomalous blip on the historical radar screen, a lost battle in a war that ultimately resulted in a win for the forces of good. The September 11th attacks merely intensified the trend. With the nation under assault from abroad, old Vietnam-era divisions seemed irrelevant. Americans of all stripes banded together in a fight against terrorism seen as unquestionably necessary and just.And then came the Iraq War. The first, so-called combat phase went well enough. Within a few weeks of crossing into Iraq, the US military had captured Baghdad and toppled Saddam Hussein. On 1 May 2003, a triumphant George W. Rush swooped onto the flight deck of the USS Abraham Lincoln and, in a now-infamous display of bravado, the navy proclaimed mission accomplished. Nothing, of course, was further from the truth. There remained the huge tasks of rooting out lingering armed resistance, rebuilding the Iraqi economy, establishing a viable post-Baathist political order, managing a nightmarish array of ethnic and religious rivalries, and winning the hearts and minds of the local population-problems that were not easily solved by the prodigious firepower and mobility that had brought the United States early success. …

A column by Lee Lawyer with stories about geophysics and geophysicists

PreviousNext You have accessThe Leading EdgeVolume 22, Issue 2A column by Lee Lawyer with stories about geophysics and geophysicistshttps://doi.org/10.1190/tle22020088.1 SectionsAboutPDF/ePub ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InRedditEmail Even though you don't see my picture at the head of this column, the war is still being waged. This is a war of nerves. Will the seven TLE Board members whose pictures you see at the beginning of this issue continue to oppose the will of the Society or will they see the light and capitulate? I have already called upon president Mike Bahorich to use this as a litmus test for future appointments. A former chairman of TLE Editorial Board has given his full support and backing for the “Bring Back the Picture” campaign.FiguresReferencesRelatedDetails Volume 22Issue 2Feb 2003Pages: 96-173ISSN (print):1070-485X ISSN (online):1938-3789 publication data© 2003 © 2003 by The Society of Exploration GeophysicistsPublisher:Society of Exploration Geophysicists HistoryPublished: 12 Jul 2017Published in print: 01 Feb 2003 CITATION INFORMATION (2003), "A column by Lee Lawyer with stories about geophysics and geophysicists," The Leading Edge 22: 88-88. https://doi.org/10.1190/tle22020088.1 Plain-Language Summary PDF Download Metrics Loading ...

Is anybody listening?

Many governments give it full backing, large budgets have been allocated to its promotion but is digital radio reaching mass audiences yet?

Distributor service excellence awards get full industry backing

Distributor service excellence awards get full industry backing

Sustaining CQI.

Angst and malaise. Dr. Z. Stern, writing on CQI in this issue of the Journal, has the prescription for health care improvement in hand, has convinced at least some of his hospital administrators and personnel of the wisdom of his approach and has started to put some antlers on the wall. Yet he is wringing his hands. Can management's commitment to CQI be sustained long enough to reap the anticipated rewards? Will physicians ever be engaged so that the benefits of CQI can be extended to the clinical realm? Fin de stick ennui and the journey has barely begun. As Dr. Stern notes, CQI has come into prominence during a prolonged crisis in health care delivery. Just as struggling industries embraced CQI in an effort to regain their competitive advantage, so hospitals have adopted CQI in the hope that it will help them reduce costs, secure contracts with payers and attract patients. In the United States, CQI has received a powerful but somewhat artificial boost by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), which has virtually mandated CQI as the workhorse of organizational improvement. However, not even the JCAHO will be able to prop up CQI for long if it produces only small, local improvements without bolstering the overall business position of hospitals. If CQI fails to deliver on the bottom line, despite full backing by management, it will prove to be — as Dr. Stern fears —just another passing fad. In essence, hospitals are engaged in a vast natural experiment of unprecedented proportions and definitive results may not be available for some time. In the meantime, management's commitment and attention can, in my view, best be preserved by following a simple CQI model that has been codified particularly clearly by Langley and Nolan [1]. This model poses three fundamental questions:

Synthesis of promin in Japan and global elimination of Hansen's disease

Prof. Morizo Ishidate synthesized "Promin" for the treatment of leprosy/Hansen's disease which had been considered "incurable" until the discovery of antileprosy effect of that drug by Dr. Faget of U.S.A. in 1941. Prof. Ishidate was the first to synthesize the drug in Japan in 1946 based on a brief news item on a Swiss journal smuggled in during the War. For this achievement, he is known as "father of chemotherapy for leprosy in Japan." Prof. Ishidate also contributed to the global fight against leprosy as the Chairman of the Board of Directors of Sasakawa Memorial Health Foundation, which he helped to establish in May 1974, with a full financial backing of Mr. Ryoichi Sasakawa, President of Japan Shipbuilding Industry Foundation. Prof. Ishidate, with his scientific knowledge as well as christianity based humanitarian concern, advised Mr. Sasakawa how to spend JSIF money wisely for eliminating leprosy and nearly US$200 million was channeled through WHO and SMHF. The successful outcome of global multidrug therapy (MDT) programme in the '80s resulted in the adoptation of resolution by the World Health Assembly, "Elimination of Leprosy, as a public health problem" by the Year 2000. The synthesis of "Promin" in Japan and promoting the global implementation of MDT, both achievement can be attributed to Prof. Ishidate.

Cardiovascular Disease Epidemiology

When Ancel Keys established the Laboratory of Physiological Hygiene at the University of Minnesota in 1946, cardiovascular disease (CVD) epidemiology did not exist. It came into being through the vision and efforts of a small group. Collaboration among the early workers developed, and by the end of the 1940s, this new branch of science was fully under way. The gate was opened by the launching of the first prospective studies, led by the Minnesota Business Men Study,1 and was soon followed by the Framingham Study.2 Keys’s contribution was decisive from the start.3 CVD epidemiology, seen as one of the major deliberate scientific approaches to atherosclerosis research, almost seemed to come from nowhere, like a nova or the “big bang.” In the late 1940s, there were forerunners, but, as always with the birth of creative ideas, there will remain some mystery around the reasons for this explosive development; it led within 30 years to coronary heart disease (CHD) becoming a largely preventable condition. The extent of this dramatic change is mirrored by the fact that the word “prevention” was not even mentioned in the report of the first symposium on CVD epidemiology, organized by Ancel Keys and Paul D. White on the occasion of the World Congress of Cardiology in Washington in 1954.4 It would seem that they saw no point in paying lip service to the self-evident target of prevention before the scientific foundations for preventive action had been laid. In those years immediately following the end of the Second World War, there was a pervasive spirit of discovery, as if to regain the time lost for scientific work during the war years. An example of how fast things moved in those days is provided by the Cooperative Study on Lipoproteins,5 a prospective study of …