Gene disruption of a G4-DNA-dependent nuclease in yeast leads to cellular senescence and telomere shortening.

The yeast gene KEM1 (also named SEP1/DST2/XRN1/RAR5) produces a G4-DNA-dependent nuclease that binds to G4 tetraplex DNA structure and cuts in a single-stranded region 5' to the G4 structure. G4-DNA generated from yeast telomeric oligonucleotides competitively inhibits the cleavage reaction, suggesting that this enzyme may interact with yeast telomeres in vivo. Homozygous deletions of the KEM1 gene in yeast block meiosis at the pachytene stage, which is consistent with the hypothesis that G4 tetraplex DNA may be involved in homologous chromosome pairing during meiosis. We conjectured that the mitotic defects of kem1/sep1 mutant cells, such as a higher chromosome loss rate, are also due to failure in processing G4-DNA, especially at telomeres. Here we report two phenotypes associated with a kem1-null allele, cellular senescence and telomere shortening, that provide genetic evidence that G4 tetraplex DNA may play a role in telomere functioning. In addition, our results reveal that chromosome ends in the same cells behave differently in a fashion dependent on the KEM1 gene product.

The bend in RNA created by the trans-activation response element bulge of human immunodeficiency virus is straightened by arginine and by Tat-derived peptide.

The trans-activation response element (TAR) found near the 5' end of the viral RNA of the human immunodeficiency virus contains a 3-nt bulge that is recognized by the virally encoded trans-activator protein (Tat), an important mediator of transcriptional activation. Insertion of the TAR bulge into double-stranded RNA is known to result in reduced electrophoretic mobility, suggestive of a bulge-induced bend. Furthermore, NMR studies indicate that Arg causes a change in the structure of the TAR bulge, possibly reducing the bulge angle. However, neither of these effects has been quantified, nor have they been compared with the effects of the TAR-Tat interaction. Recently, an approach for the quantification of bulge-induced bends has been described in which hydrodynamic measurements, employing the method of transient electric birefringence, have yielded precise estimates for the angles of a series of RNA bulges, with the angles ranging from 7 degrees to 93 degrees. In the current study, transient electric birefringence measurements indicate that the TAR bulge introduces a bend of 50 degrees +/- 5 degrees in the absence of Mg2+. Addition of Arg leads to essentially complete straightening of the helix (to < 10 degrees) with a transition midpoint in the 1 mM range. This transition demonstrates specificity for the TAR bulge: no comparable transition was observed for U3 or A3 (control) bulges with differing flanking sequences. An essentially identical structural transition is observed for the Tat-derived peptide, although the transition midpoint for the latter is near 1 microM. Finally, low concentrations of Mg2+ alone reduce the bend angle by approximately 50%, consistent with the effects of Mg2+ on other pyrimidine bulges. This last observation is important in view of the fact that most previous structural/binding studies were performed in the absence of Mg2+.

A search for anisotropy in the arrival directions of ultra high energy cosmic rays recorded at the Pierre Auger Observatory

Observations of cosmic rays arrival directions made with the Pierre Auger Observatory have previously provided evidence of anisotropy at the 99% CL using the correlation of ultra high energy cosmic rays (UHECRs) with objects drawn from the Veron-Cetty Veron catalog. In this paper we report on the use of three catalog independent methods to search for anisotropy. The 2pt-L, 2pt+ and 3pt methods, each giving a different measure of self-clustering in arrival directions, were tested on mock cosmic ray data sets to study the impacts of sample size and magnetic smearing on their results, accounting for both angular and energy resolutions. If the sources of UHECRs follow the same large scale structure as ordinary galaxies in the local Universe and if UHECRs are deflected no more than a few degrees, a study of mock maps suggests that these three method can efficiently respond to the resulting anisotropy with a P-value = 1.0% or smaller with data sets as few as 100 events. using data taken from January 1, 2004 to July 31, 2010 we examined the 20, 30, ... , 110 highest energy events with a corresponding minimum energy threshold of about 49.3 EeV. The minimum P-values found were 13.5% using the 2pt-L method, 1.0% using the 2pt+ method and 1.1% using the 3pt method for the highest 100 energy events. In view of the multiple (correlated) scans performed on the data set, these catalog-independent methods do not yield strong evidence of anisotropy in the highest energy cosmic rays.

Three Dichotomies in Lawyers’ Ethics (With Particular Attention to the Corporation as Client)

Three usually unexpressed, and too often unnoticed, conceptual dichotomies underlie our perception and understanding of lawyers’ ethics. First, the existence of a special body of professional ethics and professional regulation presupposes some special need or risk. Criminal and civil law are apparently insufficient. Ordinary day-to-day morality and ordinary ethics, likewise, are not considered to be enough. What is the risk entailed by the notion of a profession that is special; who needs protection, and from what? Two quite different possible answers to this question provide the first of the three dichotomies examined in this article: one can understand the risk as primarily to a vulnerable client from a powerful professional; or, to the contrary, from a powerful client-lawyer combination toward vulnerable others. Second, what is the foundational orientation of lawyers? Are lawyers serving primarily their particular clients, and those clients’ preferences, choices and autonomy? Or is the primary allegiance of lawyers to some community or collective goal or interest distinct from the particular goals or interests of the client? The third dichotomy concerns not the substance of the risk, or the primary orientation, but the appropriate means of responding to that risk or that fundamental obligation. Should professional ethics be implemented primarily through rules? Or, should we rely on character and the discretion of lawyers to make a thought out, all things considered, decision? Each of these three presents a fundamental difference in how we perceive and address issues of lawyers’ ethics. Each affects our understanding and analysis on multiple levels, from (1) determining the appropriate or requisite conduct in a particular situation, to (2) framing a specific rule or approach for a particular category of situations, to (3) more general or abstract theory or policy. A person’s inclinations in regard to the dichotomies affects the conclusions that person will reach on each of those levels of analysis, yet those inclinations and assumptions are frequently unexamined and unarticulated. One’s position on each of the dichotomies tends to structure the approach and outcome without the issues and choice having been explicitly addressed or possibly even noticed. This article is an effort to ameliorate that problem. Part I addresses the question of what is the risk in the work of lawyers, or the function of lawyers, for which professional ethics is the answer. The concluding section focuses on the particular problem of the corporation as client. Part II then asks the related and possibly consequent question of what is the foundational orientation or allegiance of the lawyer? Is it to the individual client? Or is it to some larger community interest? Again, the concluding section focuses on the corporation. Part III turns to the means or method for addressing the obligations and possible problems of the professional ethics of lawyers. Should lawyers’ ethics guide and confine the conduct of lawyers primarily through rules? Or should it function primarily through reliance on the knowledge, judgment and character of lawyers? If the latter were the guide, ethical decisions would be made on a situation by situation basis under the discretion of each lawyer. Toward the end of each discussion possibilities for bridging the dichotomy are considered (and with such bridges each dichotomy may come to look more like a spectrum or continuum.). At several points after its introduction in Parts I and II, the special problem of the corporation as client is revisited and possible solutions suggested. Illustrating the usefulness of keeping the dichotomies in view, Part IV applies them to several exemplary situations of ethical difficulty in actual lawyer practice. For readers finding it difficult to envision the consequences of these distinctions, turning ahead to Part IV may be useful in making the discussion more concrete. Some commonalities across the dichotomies and connections among them are then developed in the concluding section, Part V.

Three Dichotomies in Lawyers’ Ethics (With Particular Attention to the Corporation as Client)

Three usually unexpressed, and too often unnoticed, conceptual dichotomies underlie our perception and understanding of lawyers’ ethics. First, the existence of a special body of professional ethics and professional regulation presupposes some special need or risk. Criminal and civil law are apparently insufficient. Ordinary day-to-day morality and ordinary ethics, likewise, are not considered to be enough. What is the risk entailed by the notion of a profession that is special; who needs protection, and from what? Two quite different possible answers to this question provide the first of the three dichotomies examined in this article: one can understand the risk as primarily to a vulnerable client from a powerful professional; or, to the contrary, from a powerful client-lawyer combination toward vulnerable others. Second, what is the foundational orientation of lawyers? Are lawyers serving primarily their particular clients, and those clients’ preferences, choices and autonomy? Or is the primary allegiance of lawyers to some community or collective goal or interest distinct from the particular goals or interests of the client? The third dichotomy concerns not the substance of therisk, or the primary orientation, but the appropriate means of responding to that risk or that fundamental obligation. Should professional ethics be implemented primarily through rules? Or, should we rely on character and the discretion of lawyers to make a thought out, all things considered, decision? Each of these three presents a fundamental difference in how we perceive and address issues of lawyers’ ethics. Each affects our understanding and analysis on multiple levels, from (1) determining the appropriate or requisite conduct in aparticular situation, to (2) framing a specific rule or approach for a particular category of situations, to (3) more general or abstract theory or policy. A person’s inclinations in regard to the dichotomies affects the conclusions that person will reach on each of those levels of analysis, yet those inclinations and assumptions are frequently unexamined and unarticulated. One’s position on each of the dichotomies tends to structure the approach and outcome without the issues and choice having been explicitly addressed or possibly even noticed. This article is an effort to ameliorate that problem. Part I addresses the question of what is the risk in the work of lawyers, or the function of lawyers, for which professional ethics is the answer. The concluding section focuses on the particular problem of the corporation as client. Part II then asks the related and possibly consequent question of what is the foundational orientation or allegiance of the lawyer? Is it to the individual client? Or is it to some larger community interest? Again, the concluding section focuses on thecorporation. Part III turns to the means or method for addressing the obligations and possible problems of the professional ethics of lawyers. Should lawyers’ ethics guide and confine the conduct of lawyers primarily through rules? Or should it function primarily through reliance on the knowledge, judgment and character of lawyers? If the latter were the guide, ethical decisions would be made on a situation by situation basis under the discretion of each lawyer. Toward the end of each discussion possibilities for bridging the dichotomy are considered (and with such bridges each dichotomy may come to look more like a spectrum or continuum.). At several points after its introduction in Parts I and II, the special problem of the corporation as client is revisited and possible solutions suggested. Illustrating the usefulness of keeping the dichotomies in view, Part IV applies them to several exemplary situations of ethical difficulty in actual lawyer practice. For readers finding it difficult to envision the consequences of these distinctions, turning ahead to Part IV may be useful in making the discussion more concrete. Some commonalities across the dichotomies and connections among them are then developed in the concluding section, Part V.

A first approach to earthquake damage estimation in Haiti: advices to minimize the seismic risk

This study is in the frame of the cooperative line that several Spanish Universities and other foreign partners started with the Haitian government in 2010. According to our studies (Benito et al. in An evaluation of seismic hazard in La Hispaniola, after the 2010 Haiti earthquake, 33rd General Assembly of the European Seismological Commission, Moscow, Russia, 2012) and recent scientific literature, the earthquake hazard in Haiti remains high (Calais et al. in Nat Geosci 3:794–799, 2010). In view of this, we wonder whether the country is currently ready to face another earthquake. In this sense, we estimated several damage scenarios in Port-au-Prince and Cap-Haitien associated to realistic possible major earthquakes. Our findings show that almost 50 % of the building stock of both cities would result uninhabitable due to structural damage. Around 80 % of the buildings in both cities have reinforced concrete structure with concrete block infill; however, the presence of masonry buildings becomes significant (between 25 and 45 % of the reinforced concrete buildings) in rural areas and informal settlements on the outskirts, where the estimated damage is higher. The influence of the soil effect on the damage spatial distribution is evident in both cities. We have found that the percentage of uninhabitable buildings in soft soil areas may be double the percentage obtained in nearby districts located in hard soil. These results reveal that a new seismic catastrophe of similar or even greater consequences than the 2010 Haiti earthquake might happen if the earthquake resilience is not improved in the country. Nowadays, the design of prevention actions and mitigation policies is the best instrument the society has to face seismic risk. In this sense, the results of this research might contribute to define measures oriented to earthquake risk reduction in Haiti, which should be a real priority for national and international institutions.

Diary of Elias Mann, 1796-1800

Elias Mann kept this diary during his undergraduate years at Harvard College. The diary begins August 17, 1796 and ends in August of 1800 and also includes several undated sheets filled with excerpts of poems. The daily entries describe many aspects of Mann's life, including not only his experiences at Harvard but also his involvement in the larger community. Entries related to life at Harvard describe club meetings (coffee club, Hasty Pudding Club and Phi Beta Kappa); trips to the theater; dinners at taverns; games and recreation, including a card game called "Loo," cribbage, backgammon, bowling, playing ball, fishing, skating and going for sleigh rides; gathering, and sometimes taking from others' gardens, food (most often plums, peaches, nuts and apples); what he ate (including one breakfast of three raw eggs and two glasses of wine); what he read (including Tristram Shandy and one of "Mrs. Ratcliffe's novels"); his friends, often mentioned by name; and academic work and formalities. In one entry he mentions the theft of several possessions from his room, and there are several entries about trips to Fresh Pond.

Fī bayān mā dhakarahu Muḥammad Afandī al-Awaljī al-marsūl min ṭaraf al-dawlah al-ʻalīyah ilá Faransā wa-mā shāhadahu hunāk =: Traduction arabe de la relation de voyage en France de Mehmet Effendi, Ambassadeur de Turquie : manuscript, undated

بيان ما ذكره محمد افندي المرسول من طرف الدولة العلية إلى فرنسا وجميع ما شاهده هناك قال انه... :Incipit

Zafer-nâme / li-Karaçelebizade Abdülaziz Efendi : manuscript, 1723 or 4

A historical account of the Yerevan and Baghdad campaigns of Murād IV (r. 1623-1640). Composed in eight chapters. Book begins in 1044 AH [1635 AD] with the army setting out from Üsküdar and ends in 1049 AH [1640 AD] with the sultna's return to Istanbul after conclusion of Kasrışirin Treaty.

Hādhā kitāb Tuḥfat al-mulūk : manuscript, 1658

A short treatise on Ḥanafī fiqh.

Saving the Monopsony: Exclusivity, Innovation and Market Power in the Media Sector. Research Papers in Law, 7/2006

From the Introduction. The Media Sector has experienced a technological revolution in the last 15 years. Digital encoding of television signals made possible a more efficient use of the radiospectrum. Digital terrestrial television (hereinafter, “DTT”) allows now for the reception of a significant number of free-to-air channels.1 Moreover, the use of new transmission platforms (hereinafter,“platforms”), namely cable and direct-to-home satellite (hereinafter, “DTH”) paved the way for the arrival in Europe of pay-TV operators, which finance their activities mainly via subscription fees. This changing technological landscape is subject to further evolution in the near future, as incumbent telecommunications operators become increasingly interested in making available broadcasting content2 as part of their broadband offer and 3G mobile handsets can be used for the reception of TV signals....The present paper seeks to ascertain whether the Commission “regulatory approach” towards the exclusive sale of premium content is a sound one, in particular in view of the constant technological evolution outlined above. The assumptions underlying landmark Commission decisions will be compared with recent developments of the media sector in Italy. In the NewsCorp./Telepiù case, decided in 2003, the Commission imposed very strict conditions to allow the merger giving birth to Sky Italia, on the assumption that the operation created a lasting near-monopsony in the different upstream markets for the acquisition of premium intervened against the media conglomerate Mediaset (which controls, inter alia, the main three private free-to-air channels in Italy) for an alleged abuse of dominant position.17 In fact, and contrary to the forecasts made by the Commission, Mediaset was in a position to acquire the broadcasting rights of the main Italian football teams, thereby excluding the incumbent (and near-monopolist) pay-TV operator, Sky Italia. This may go to show that the reality of the sector is more complex and evolves faster than one may infer from the Commission practice, thus putting into question its stance regarding exclusivity. The experience of the evolution of the Italian media sector will be used as the starting point for the evaluation of alternative regulatory options.

Legal Aspects in Establishing the Internal Market for services. Research Papers in Law, 6/2007

Introduction. The internal market for services is one of the objectives set by the founding fathers of the EC back in 1957. It is only in the last ten-fifteen years, however, that this aspect of the internal market has seriously attracted the attention of the EC legislature and judiciary.1 With the exception of some sector-specific directives dating back in the late ‘80s, it is only with the deregulation of network industries, the development of electronic communications and the spread of financial services, in the ‘90s that substantial bits of legislation got adopted in the field of services. Similarly, the European Court of Justice (ECJ, the Court) left the principles established in Van Binsbergen back in 1973, hibernate for a long time before fully applying them in Säger and constantly thereafter.2 Ever since, the Court’s case law in this field has grown so important that it has become the compulsory starting point for any study concerning the (horizontal) regulation of the internal market in services. The limits inherent to negative integration and to the casuistic approach pursued by judiciary decisions have prompted the need for a general legislative text to be adopted for services in the internal market. This text, however, hotly debated both at the political and at the legal level, has ended up in little more than a complex restatement of the Court’s case law. It may be, however, that this ‘little more’ is not that little. In view of the ever expanding application of the Treaty rules on services, promoted by the ECJ (para. 1),3 the Directive certainly appears to be a limited regulatory attempt (para. 2). This, however, does not mean that the Directive is a toothless, or useless regulatory instrument (conclusion: para. 3).

The importance of International Developments in the case-law of the European Court of Justice: Kadi and the autonomy of the EC legal order. Research Papers in Law, 1/2009

From the Introduction. In the USA, the debate is still ongoing as to whether and to what extent the Supreme Court could or should refer to foreign precedent, in particular in relation to constitutional matters such as the death penalty.1 In the EU, in particular the recent Kadi case of 20082 has triggered much controversy,3 thereby highlighting the opposite angle to a similar discussion. The focus of attention in Europe is namely to what extent the European Court of Justice (hereafter “ECJ”) could lawfully and rightfully refuse to plainly ‘surrender’ or to subordinate the EC legal system to UN law and obligations when dealing with human rights issues. This question becomes all the more pertinent in view of the fact that in the past the ECJ has been rather receptive and constructive in forging interconnectivity between the EC legal order and international law developments. A bench mark in that respect was undoubtedly the Racke case of 1998,4 where the ECJ spelled out the necessity for the EC to respect international law with direct reference to a ruling of the International Court of Justice. This judgment which was rendered 10 years earlier than Kadi equally concerned EC/EU economic sanctions taken in implementation of UN Security Council Resolutions. A major question is therefore whether it is at all possible, and if so to determine how, to reconcile those apparently conflicting judgments.

The Composition and Drivers of Energy Prices and Costs in Energy-Intensive Industries: The Case of Ceramics, Glass and Chemicals. CEPS Special Report No. 85, 27 March 2014

In May 2013, the European Commission received a mandate from the European Council to “to present an analysis of the composition and drivers of energy prices and costs in Member States, with a particular focus on the impact on households, SMEs and energy intensive industries, and looking more widely at the EU's competitiveness vis-à-vis its global economic counterparts”. Following such mandate and in view of the preparation by the Commission of a Communication and a Staff Working Document, DG Enterprise and Industry commissioned CEPS to carry out a set of studies aimed at providing well-grounded evidence about the evolution and composition of energy prices and costs at plant level within individual industry sectors. A team of CEPS researchers conducted the research, led by Christian Egenhofer and Lorna Schrefler. Vasileios Rizos served as Project Coordinator. Other CEPS researchers contributing to the project included: Fabio Genoese, Andrea Renda, Andrei Marcu, Julian Wieczorkiewicz, Susanna Roth, Federico Infelise, Giacomo Luchetta, Lorenzo Colantoni, Wijnand Stoefs, Jacopo Timini and Felice Simonelli. In addition to an introductory report entitled “About the Study and Cross-Sectoral Analysis”, CEPS prepared five sectoral case studies: two on ceramics (wall and floor tiles and bricks and roof tiles), two on chemicals (ammonia and chlorine) and one on flat glass. Each of these six studies has been consolidated in this single volume for free downloading on the CEPS website. The specific objective was to complement information already available at macro level with a bottom-up perspective on the operating conditions that industry stakeholders need to deal with, in terms of energy prices and costs. The approach chosen was based on case studies for a selected set (sub-)sectors amongst energy-intensive industries. A standard questionnaire was circulated and respondents were sampled according to specified criteria. Data and information collected were finally presented in a structured format in order to guarantee comparability of results between the different (sub-)sectors analysed. The complete set of files can also be downloaded from the European Commission’s website: http://ec.europa.eu/enterprise/newsroom/cf/itemdetail.cfm?item_id=7238&lang=en&title=Study-on-composition-and-drivers-of-energy-prices-and-costs-in-energy-intnsive-industries The results of the studies were presented at a CEPS Conference held on February 26th along with additional evidence from other similar studies. The presentations can be downloaded at: http://www.ceps.eu/event/level-and-drivers-eu-energy-prices-energy-inten...

Bail-in Provisions in State Aid and Resolution Procedures: Are they consistent with systemic stability? CEPS Policy Brief No. 318, 21 May 2014

This CEPS Policy Brief examines the provisions for bail-in in the European Union – that is, the principle whereby any public measure to recapitalise a bank with insufficient prudential capital must be preceded by a write-down or conversion into equity of creditors’ claims – in state aid policies and in the new resolution framework for failing banks, with two aims: i) to assess whether and how they are coordinated and ii) more importantly, whether they address satisfactorily the question of systemic stability that may arise when investors fear that creditors’ claims are likely to be bailed-in in a bank crisis. The issue is especially relevant in the present context, as the comprehensive assessment exercise underway for EU banks falling under the direct supervision of the European Central Bank may lead supervisors to require substantial capital injections simultaneously for many of the banks involved, possibly shaking investors’ confidence across EU banking markets. The authors conclude that the two sets of rules are, broadly speaking, mutually consistent and that they already contain sufficient safeguards to address systemic stability concerns. However, the balance of the elements underpinning the European Commission’s decisions in individual cases may not be clear to bank creditors and potential investors in financial markets. The impression of unneeded rigidity on this very sensitive issue has been heightened by official statements over-emphasising that each case will be assessed individually under competition rules, thus feeding the concern that the systemic dimension of the issue may have been underestimated. Therefore, further clarification by the Commission may be needed on how the various criteria will be applied during the ongoing transition to banking union – perhaps through a new communication completing the state aid framework for banks in view of the adoption of the new resolution rules.