Turing and the Trans-Pacific Partnership: Intellectual Property, Public Health, and Access to Essential Medicines

A recent controversy in the United States over drug pricing by Turing Pharmaceuticals AG has raised larger issues in respect of intellectual property, access to medicines, and the Trans-Pacific Partnership (TPP). In August 2015, Turing Pharmaceuticals AG – a private biopharmaceutical company with offices in New York, the United States, and Zug, Switzerland - acquired the exclusive marketing rights to Daraprim in the United States from Impax Laboratories Incorporated. Martin Shkreli, Turing’s Founder and Chief Executive Officer, maintained: “The acquisition of Daraprim and our toxoplasmosis research program are significant steps along Turing’s path of bringing novel medications to patients with serious disorders, some of whom often go undiagnosed and untreated.” He emphasised: “We intend to invest in the development of new drug candidates that we hope will yield an even better clinical profile, and also plan to launch an educational effort to help raise awareness and improve diagnosis for patients with toxoplasmosis.” In September 2015, there was much public controversy over the decision of Martin Shkreli to raise the price of a 62 year old drug, Daraprim, from $US13.50 to $US750 a pill. The drug is particularly useful in respect to the treatment and prevention of malaria, and in the treatment of infections in individuals with HIV/AIDS. Daraprim is listed on the World Health Organization’s (WHO) List of Essential Medicines. In the face of much criticism, Martin Shkreli has said that he will reduce the price of Daraprim. He observed: “We've agreed to lower the price on Daraprim to a point that is more affordable and is able to allow the company to make a profit, but a very small profit.” He maintained: “We think these changes will be welcomed.” However, he has been vague and ambiguous about the nature of the commitment. Notably, the lobby group, Pharmaceutical Research and Manufacturers of America (PhARMA), disassociated itself from the claims of Turing Pharmaceuticals. The group said: “PhRMA members have a long history of drug discovery and innovation that has led to increased longevity and improved lives for millions of patients.” The group noted: “Turing Pharmaceutical is not a member of PhRMA and we do not embrace either their recent actions or the conduct of their CEO.” The biotechnology peak body Biotechnology Industry Organization also sought to distance itself from Turing Pharmaceuticals. A hot topic: United States political debate about access to affordable medicines This controversy over Daraprim is unusual – given the age of drug concerned. Daraprim is not subject to patent protection. Nonetheless, there remains a monopoly in respect of the marketplace. Drug pricing is not an isolated problem. There have been many concerns about drug pricing – particularly in respect of essential medicines for HIV/AIDS, tuberculosis, and malaria. This recent controversy is part of a larger debate about access to affordable medicines. The dispute raises larger issues about healthcare, consumer rights, competition policy, and trade. The Daraprim controversy has provided impetus for law reform in the US. US Presidential Candidate Hillary Clinton commented: “Price gouging like this in this specialty drug market is outrageous.” In response to her comments, the Nasdaq Biotechnology Index fell sharply. Hillary Clinton has announced a prescription drug reform plan to protect consumers and promote innovation – while putting an end to profiteering. On her campaign site, she has emphasised that “affordable healthcare is a basic human right.” Her rival progressive candidate, Bernie Sanders, was also concerned about the price hike. He wrote a letter to Martin Shkreli, complaining about the price increase for the drug Daraprim. Sanders said: “The enormous, overnight price increase for Daraprim is just the latest in a long list of skyrocketing price increases for certain critical medications.” He has pushed for reforms to intellectual property to make medicines affordable. The TPP and intellectual property The Daraprim controversy and political debate raises further issues about the design of the TPP. The dispute highlights the dangers of extending the rights of pharmaceutical drug companies under intellectual property, investor-state dispute settlement, and drug administration. Recently, the civil society group Knowledge Ecology International published a leaked draft of the Intellectual Property Chapter of the TPP. Knowledge Ecology International Director, James Love, was concerned the text revealed that the US “continues to be the most aggressive supporter of expanded intellectual property rights for drug companies.” He was concerned that “the proposals contained in the TPP will harm consumers and in some cases block innovation.” James Love feared: “In countless ways, the Obama Administration has sought to expand and extend drug monopolies and raise drug prices.” He maintained: “The astonishing collection of proposals pandering to big drug companies make more difficult the task of ensuring access to drugs for the treatment of cancer and other diseases and conditions.” Love called for a different approach to intellectual property and trade: “Rather than focusing on more intellectual property rights for drug companies, and a death-inducing spiral of higher prices and access barriers, the trade agreement could seek new norms to expand the funding of medical research and development (R&D) as a public good, an area where the US has an admirable track record, such as the public funding of research at the National Institutes of Health (NIH) and other federal agencies.” In addition, there has been much concern about the Investment Chapter of the TPP. The investor-state dispute settlement regime would enable foreign investors to challenge government policy making, which affected their investments. In the context of healthcare, there is a worry that pharmaceutical drug companies will deploy their investor rights to challenge public health measures – such as, for instance, initiatives to curb drug pricing and profiteering. Such concerns are not merely theoretical. Eli Lilly has brought an investor action against the Canadian Government over the rejection of its drug patents under the investor-state dispute settlement regime of the North American Free Trade Agreement (NAFTA). The Health Annex to the TPP also raises worries that pharmaceutical drug companies will able to object to regulatory procedures in respect of healthcare. It is disappointing that the TPP – in the leaks that we have seen – has only limited recognition of the importance of access to essential medicines. There is a need to ensure that there are proper safeguards to provide access to essential medicines – particularly in respect of HIV/AIDs, malaria, and tuberculosis. Moreover, there must be protection against drug profiteering and price gouging in any trade agreement. There should be strong measures against the abuse of intellectual property rights. The dispute over Turing Pharmaceuticals AG and Daraprim is an important cautionary warning in respect of some of the dangers present in the secret negotiations in respect of the TPP. There is a need to preserve consumer rights, competition policy, and public health in trade negotiations over an agreement covering the Pacific Rim.

Now the real international fight begins for the Trans-Pacific Partnership

In Atlanta, the trade ministers of a dozen countries across the Pacific Rim announced that they had successfully reached a concluded agreement upon the Trans-Pacific Partnership. The debate over the TPP will now play out in legislatures across the Pacific Rim, where sentiment towards the deal is much more mixed. The ministers insisted: “After more than five years of intensive negotiations, we have come to an agreement that will support jobs, drive sustainable growth, foster inclusive development, and promote innovation across the Asia-Pacific region … The agreement achieves the goal we set forth of an ambitious, comprehensive, high standard and balanced agreement that will benefit our nation’s citizens … We expect this historic agreement to promote economic growth, support higher-paying jobs; enhance innovation, productivity and competitiveness; raise living standards; reduce poverty in our countries; and to promote transparency, good governance, and strong labor and environmental protections.” But there has been fierce criticism of the Trans-Pacific Partnership, because of both its secrecy and its substance. Nobel Laureate Professor Joseph Stiglitz has warned that the agreement is not about free trade, but about the protection of corporate monopolies. The intellectual property chapter provides for longer and stronger protection of intellectual property rights. The investment chapter provides foreign investors with the power to challenge governments under an investor-state dispute settlement (ISDS) regime. The environment chapter is weak and toothless, and seems to be little more than an exercise in greenwashing. The health annex — and many other parts of the agreement — strengthen the power of pharmaceutical companies and biotechnology developers. The text on state-owned enterprises raises concerns about public ownership of postal services, broadcasters and national broadband services.

The Trans-Pacific partnership protects old companies at the expense of the new

Under this trade agreement, intellectual property will be transformed into a means of protecting the investments of multinational companies in culture, advertising, and medicine, writes Matthew Rimmer. The Trans-Pacific Partnership (TPP) is a blockbuster trade deal, which will transform the intellectual property of the Pacific Rim. The Australian Prime Minister Malcolm Turnbull has argued the trade agreement is a "gigantic foundation stone" for the country's future prosperity. Nonetheless, though the final text remains unreleased, it's clear from what we do know that the Intellectual Property Chapter is set to protect legacy intellectual property industries - rather than support disruptive technologies and dynamic innovation.

The Trans-Pacific Partnership, Copyright Law and Education

There is much concern across the Pacific rim about the impact of the Trans-Pacific Partnership (TPP) upon public education. The secretive trade agreement involves a dozen nations across the Pacific, including Australia, New Zealand, Canada and the United States, and Indonesia may soon join. Although the text was finalised at the Atlanta talks in October 2015, the Agreement has not yet been made public. (The NTEU has joined with other unions and civil society organisations in calling for the agreement to be revealed to facilitate public debate before any decisions are made by Parliament.) So whilst we cannot examine all the text that may impact on public educations, WikiLeaks has published the final version of the Intellectual Property Chapter of the TPP. The Intellectual Property Chapter of the TPP alone, with its copyright term extension, limits on copyright exceptions, and enforcement measures, will have a significant impact for educators and public education.

The Trans-Pacific Partnership Poses a Grave Threat to Sustainable Development

This month’s long-awaited release of the Trans-Pacific Partnership (TPP) text was the result of years of negotiations on trade ties between nations around the Pacific Rim. Some six weeks earlier, another set of deliberations came to an end as the United Nations unveiled its 17 Sustainable Development Goals (SDGs), which aim to eradicate poverty and reduce inequality by addressing critical issues such as food security, health care, access to education, clean and affordable water, clean energy, and climate action. Unfortunately, the two documents are incompatible. Several chapters of the TPP impinge upon the SDGs, potentially undermining the UN’s efforts to promote sustainable development and equality throughout the Pacific region. Moreover, many developing countries, least-developed countries, and small island states in the Pacific region are excluded from the preferential trade deal.

Recommendation of Multimedia Objects Using Metadata and Link Analysis

We investigate methods for recommending multimedia items suitable for an online multimedia sharing community and introduce a novel algorithm called UserRank for ranking multimedia items based on link analysis. We also take the initiative of applying EigenRumor from the domain of blogosphere to multimedia. Furthermore, we present a strategy for making personalized recommendation that combines UserRank with collaborative filtering. We evaluate our method with an informal user study and show that results obtained are promising.

Greenwashing the Trans-Pacific Partnership: Fossil fuels, the environment, and climate change

There has been much controversy over the Trans-Pacific Partnership (TPP) – a plurilateral trade agreement involving a dozen nations from throughout the Pacific Rim – and its impact upon the environment, biodiversity, and climate change. The secretive treaty negotiations involve Australia and New Zealand; countries from South East Asia such as Brunei Darussalam, Malaysia, Singapore, Vietnam, and Japan; the South American nations of Peru and Chile; and the members of the 1994 North American Free Trade Agreement (NAFTA), Canada, Mexico and the United States. There was an agreement reached between the parties in October 2015. The participants asserted: ‘We expect this historic agreement to promote economic growth, support higher-paying jobs; enhance innovation, productivity and competitiveness; raise living standards; reduce poverty in our countries; and to promote transparency, good governance, and strong labor and environmental protections.’ The final texts of the agreement were published in November 2015. There has been discussion as to whether other countries – such as Indonesia, the Philippines, and South Korea – will join the deal. There has been much debate about the impact of this proposed treaty upon intellectual property, the environment, biodiversity and climate change. There have been similar concerns about the Trans-Atlantic Trade and Investment Partnership (TTIP) – a proposed trade agreement between the United States and the European Union. In 2011, the United States Trade Representative developed a Green Paper on trade, conservation, and the environment in the context of the TPP. In its rhetoric, the United States Trade Representative has maintained that it has been pushing for strong, enforceable environmental standards in the TPP. In a key statement in 2014, the United States Trade Representative Mike Froman insisted: ‘The United States’ position on the environment in the Trans-Pacific Partnership negotiations is this: environmental stewardship is a core American value, and we will insist on a robust, fully enforceable environment chapter in the TPP or we will not come to agreement.’ The United States Trade Representative maintained: ‘Our proposals in the TPP are centered around the enforcement of environmental laws, including those implementing multilateral environmental agreements (MEAs) in TPP partner countries, and also around trailblazing, first-ever conservation proposals that will raise standards across the region’. Moreover, the United States Trade Representative asserted: ‘Furthermore, our proposals would enhance international cooperation and create new opportunities for public participation in environmental governance and enforcement.’ The United States Trade Representative has provided this public outline of the Environment Chapter of the TPP: A meaningful outcome on environment will ensure that the agreement appropriately addresses important trade and environment challenges and enhances the mutual supportiveness of trade and environment. The Trans-Pacific Partnership countries share the view that the environment text should include effective provisions on trade-related issues that would help to reinforce environmental protection and are discussing an effective institutional arrangement to oversee implementation and a specific cooperation framework for addressing capacity building needs. They also are discussing proposals on new issues, such as marine fisheries and other conservation issues, biodiversity, invasive alien species, climate change, and environmental goods and services. Mark Linscott, an assistant Trade Representative testified: ‘An environment chapter in the TPP should strengthen country commitments to enforce their environmental laws and regulations, including in areas related to ocean and fisheries governance, through the effective enforcement obligation subject to dispute settlement.’ Inside US Trade has commented: ‘While not initially expected to be among the most difficult areas, the environment chapter has emerged as a formidable challenge, partly due to disagreement over the United States proposal to make environmental obligations binding under the TPP dispute settlement mechanism’. Joshua Meltzer from the Brookings Institute contended that the trade agreement could be a boon for the protection of the environment in the Pacific Rim: Whether it is depleting fisheries, declining biodiversity or reduced space in the atmosphere for Greenhouse Gas emissions, the underlying issue is resource scarcity. And in a world where an additional 3 billion people are expected to enter the middle class over the next 15 years, countries need to find new and creative ways to cooperate in order to satisfy the legitimate needs of their population for growth and opportunity while using resources in a manner that is sustainable for current and future generations. The TPP parties already represent a diverse range of developed and developing countries. Should the TPP become a free trade agreement of the Asia-Pacific region, it will include the main developed and developing countries and will be a strong basis for building a global consensus on these trade and environmental issues. The TPP has been promoted by its proponents as a boon to the environment. The United States Trade Representative has maintained that the TPP will protect the environment: ‘The United States’ position on the environment in the TPP negotiations is this: environmental stewardship is a core American value, and we will insist on a robust, fully enforceable environment chapter in the TPP or we will not come to agreement.’ The United States Trade Representative discussed ‘Trade for a Greener World’ on World Environment Day. Andrew Robb, at the time the Australian Trade and Investment Minister, vowed that the TPP will contain safeguards for the protection of the environment. In November 2015, after the release of the TPP text, Rohan Patel, the Special Assistant to the President and Deputy Director of Intergovernmental Affairs, sought to defend the environmental credentials of the TPP. He contended that the deal had been supported by the Nature Conservancy, the International Fund for Animal Welfare, the Joint Ocean Commission Initiative, the World Wildlife Fund, and World Animal Protection. The United States Congress, though, has been conflicted by the United States Trade Representative’s arguments about the TPP and the environment. In 2012, members of the United States Congress - including Senator Ron Wyden (D-OR), Olympia Snowe (R-ME), and John Kerry (D-MA) – wrote a letter, arguing that the trade agreement needs to provide strong protection for the environment: ‘We believe that a '21st century agreement' must have an environment chapter that guarantees ongoing sustainable trade and creates jobs, and this is what American businesses and consumers want and expect also.’ The group stressed that ‘A binding and enforceable TPP environment chapter that stands up for American interests is critical to our support of the TPP’. The Congressional leaders maintained: ‘We believe the 2007 bipartisan congressional consensus on environmental provisions included in recent trade agreements should serve as the framework for the environment chapter of the TPP.’ In 2013, senior members of the Democratic leadership expressed their opposition to granting President Barack Obama a fast-track authority in respect of the TPP House of Representatives Minority Leader Nancy Pelosi said: ‘No on fast-track – Camp-Baucus – out of the question.’ Senator Majority leader Harry Reid commented: ‘I’m against Fast-Track: Everyone would be well-advised to push this right now.’ Senator Elizabeth Warren has been particularly critical of the process and the substance of the negotiations in the TPP: From what I hear, Wall Street, pharmaceuticals, telecom, big polluters and outsourcers are all salivating at the chance to rig the deal in the upcoming trade talks. So the question is, Why are the trade talks secret? You’ll love this answer. Boy, the things you learn on Capitol Hill. I actually have had supporters of the deal say to me ‘They have to be secret, because if the American people knew what was actually in them, they would be opposed. Think about that. Real people, people whose jobs are at stake, small-business owners who don’t want to compete with overseas companies that dump their waste in rivers and hire workers for a dollar a day—those people, people without an army of lobbyists—they would be opposed. I believe if people across this country would be opposed to a particular trade agreement, then maybe that trade agreement should not happen. The Finance Committee in the United States Congress deliberated over the Trans-Pacific Partnership negotiations in 2014. The new chair Ron Wyden has argued that there needs to be greater transparency in trade. Nonetheless, he has mooted the possibility of a ‘smart-track’ to reconcile the competing demands of the Obama Administration, and United States Congress. Wyden insisted: ‘The new breed of trade challenges spawned over the last generation must be addressed in imaginative new policies and locked into enforceable, ambitious, job-generating trade agreements.’ He emphasized that such agreements ‘must reflect the need for a free and open Internet, strong labor rights and environmental protections.’ Elder Democrat Sander Levin warned that the TPP failed to provide proper protection for the environment: The TPP parties are considering a different structure to protect the environment than the one adopted in the May 10 Agreement, which directly incorporated seven multilateral environmental agreements into the text of past trade agreements. While the form is less important than the substance, the TPP must provide an overall level of environmental protection that upholds and builds upon the May 10 standard, including fully enforceable obligations. But many of our trading partners are actively seeking to weaken the text to the point of falling short of that standard, including on key issues like conservation. Nonetheless, 2015, President Barack Obama was able to secure the overall support of the United States Congress for his ‘fast-track’ authority. This was made possible by the Republicans and dissident Democrats. Notably, Oregon Senator Ron Wyden switched sides, and was transformed from a critic of the TPP to an apologist for the TPP. For their part, green political parties and civil society organisations have been concerned about the secretive nature of the negotiations; and the substantive implications of the treaty for the environment. Environmental groups and climate advocates have been sceptical of the environmental claims made by the White House for the TPP. The Green Party of Aotearoa New Zealand, the Australian Greens and the Green Party of Canada have released a joint declaration on the TPP observing: ‘More than just another trade agreement, the TPP provisions could hinder access to safe, affordable medicines, weaken local content rules for media, stifle high-tech innovation, and even restrict the ability of future governments to legislate for the good of public health and the environment’. In the United States, civil society groups such as the Sierra Club, Public Citizen, WWF, the Friends of the Earth, the Rainforest Action Network and 350.org have raised concerns about the TPP and the environment. Allison Chin, President of the Sierra Club, complained about the lack of transparency, due process, and public participation in the TPP talks: ‘This is a stealth affront to the principles of our democracy.’ Maude Barlow’s The Council of Canadians has also been concerned about the TPP and environmental justice. New Zealand Sustainability Council executive director Simon Terry said the agreement showed ‘minimal real gains for nature’. A number of organisations have joined a grand coalition of civil society organisations, which are opposed to the grant of a fast-track. On the 15th January 2013, WikiLeaks released the draft Environment Chapter of the TPP - along with a report by the Chairs of the Environmental Working Group. Julian Assange, WikiLeaks' publisher, stated: ‘Today's WikiLeaks release shows that the public sweetener in the TPP is just media sugar water.’ He observed: ‘The fabled TPP environmental chapter turns out to be a toothless public relations exercise with no enforcement mechanism.’ This article provides a critical examination of the draft Environment Chapter of the TPP. The overall argument of the article is that the Environment Chapter of the TPP is an exercise in greenwashing – it is a public relations exercise by the United States Trade Representative, rather than a substantive regime for the protection of the environment in the Pacific Rim. Greenwashing has long been a problem in commerce, in which companies making misleading and deceptive claims about the environment. In his 2012 book, Greenwash: Big Brands and Carbon Scams, Guy Pearse considers the rise of green marketing and greenwashing. Government greenwashing is also a significant issue. In his book Storms of My Grandchildren, the climate scientist James Hansen raises his concerns about government greenwashing. Such a problem is apparent with the TPP – in which there was a gap between the assertions of the United States Government, and the reality of the agreement. This article contends that the TPP fails to meet the expectations created by President Barack Obama, the White House, and the United States Trade Representative about the environmental value of the agreement. First, this piece considers the relationship of the TPP to multilateral environmental treaties. Second, it explores whether the provisions in respect of the environment are enforceable. Third, this article examines the treatment of trade and biodiversity in the TPP. Fourth, this study considers the question of marine capture fisheries. Fifth, there is an evaluation of the cursory text in the TPP on conservation. Sixth, the article considers trade in environmental services under the TPP. Seventh, this article highlights the tensions between the TPP and substantive international climate action. It is submitted that the TPP undermines effective and meaningful government action and regulation in respect of climate change. The conclusion also highlights that a number of other chapters of the TPP will impact upon the protection of the environment – including the Investment Chapter, the Intellectual Property Chapter, the Technical Barriers to Trade Chapter, and the text on public procurement.

From mundane to smart: Exploring interactions with ‘smart' design objects

In addition to functional and technological features, the role of augmented objects should also be seen in terms of how effectively they fit into the everyday practices of users and how they enhance users' experiences. In this article, the authors introduce a low-tech, internet-of-things technology called CAM (Cooperative Artefact Memory) that is used as a collaborative tool in design studio environments. CAM works as an object memory technology and allows industrial and product designers to collaboratively store relevant information onto their physical design objects, such as sketches, collages, storyboards, and physical mock-ups in the form of messages, annotations and external web links. In the context of this study, CAM serves as an important probing device to understand designers' interaction and experiences with augmented design objects, in their natural environment. The authors carried out a small-scale field trial of CAM in an academic design studio, over three student design projects. In this article, they discuss the findings of their field trial and show how CAM was used by the participants, how it was integrated into the design process and how it was appropriated for different purposes. The authors also found that CAM supported coordination and awareness within the design teams, yet its serendipitous and asynchronous nature facilitated creative and playful interactions between team members. In general, the results show how CAM transformed mundane design objects into “smart” objects that made the creative and playful side of cooperative design visible.

Conformations of Heterochiral and Homochiral Proline-Pseudoproline Segments in Peptides: Context Dependent Cis-Trans Peptide Bond Isomerization

The pseudoproline residue (Psi Pro, L-2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid) has been introduced into heterochiral diproline segments that have been previously shown to facilitate the formation of beta-hairpins, containing central two and three residue turns. NMR studies of the octapeptide Boc-Leu-Phe-Val-(D)Pro-Psi Pro-Leu-Phe-Val-OMe (1), Boc-Leu-Val-Val-(D)Pro-Psi Pro-Leu-Val-Val-OMe (2), and the nonapeptide sequence Boc-Leu-Phe-Val-(D)Pro-Psi Pro-(D)Ala-Leu-Phe-Val-OMe (3) established well-registered beta-hairpin structures in chloroform solution, with the almost exclusive population of the trans conformation for the peptide bond preceding the Psi Pro residue. The beta-hairpin conformation of 1 is confirmed by single crystal X-ray diffraction. Truncation of the strand length in Boc-Val-(D)Pro-Psi Pro-Leu-OMe (4) results in air increase in the population of the cis conformer, with a cis/trans ratio of 3.65. Replacement of Psi Pro in 4 by (L)Pro in 5, results in almost exclusive population of the trans form, resulting in an incipient beta-hairpin conformation, stabilized by two intramolecular hydrogen bonds. Further truncation of the sequence gives an appreciable rise in the population of cis conformers in the tripeptide piv-(D)Pro-Psi Pro-Leu-OMe (6). In the homochiral segment Piv-Pro Psi Pro-Leu-OMe (7) only the cis form is observed with the NMR evidence strongly supporting a type VIa beta-turn conformation, stabilized by a 4 -> 1 hydrogen bond between the Piv (CO) and Leu (3) NH groups. The crystal structure of the analog peptide 7a (Piv-Pro-Psi(H,CH3)Pro-Leu-NHMe) confirms the cis peptide bond geometry for the Pro-Psi(H,CH3)pro peptide bond, resulting in a type VIa beta-turn conformation.

trans gene regulation in adaptive evolution: A genetic algorithm model

This is a continuation of earlier studies on the evolution of infinite populations of haploid genotypes within a genetic algorithm framework. We had previously explored the evolutionary consequences of the existence of indeterminate—“plastic”—loci, where a plastic locus had a finite probability in each generation of functioning (being switched “on”) or not functioning (being switched “off”). The relative probabilities of the two outcomes were assigned on a stochastic basis. The present paper examines what happens when the transition probabilities are biased by the presence of regulatory genes. We find that under certain conditions regulatory genes can improve the adaptation of the population and speed up the rate of evolution (on occasion at the cost of lowering the degree of adaptation). Also, the existence of regulatory loci potentiates selection in favour of plasticity. There is a synergistic effect of regulatory genes on plastic alleles: the frequency of such alleles increases when regulatory loci are present. Thus, phenotypic selection alone can be a potentiating factor in a favour of better adaptation.

Stereochemical studies on cyclic peptides: Detailed energy minimization studies on hydrogen bonded all-trans cyclic pentapeptide backbones

Conformational studies have been carried out on hydrogenbonded all-trans cyclic pentapeptide backbone. Application of a combination of grid search and energy minimization on this system has resulted in obtaining 23 minimum energy conformations, which are characterized by unique patterns of hydrogen bonding comprising of β- and γ-turns. A study of the minimum energy conformationsvis-a-vis non-planar deviation of the peptide units reveals that non-planarity is an inherent feature in many cases. A study on conformational clustering of minimum energy conformations shows that the minimum energy conformations fall into 6 distinct conformational families. Preliminary comparison with available X-ray structures of cyclic pentapeptide indicates that only some of the minimum energy conformations have formed crystal structures. The set of minimum energy conformations worked out in the present study can form a consolidated database of prototypes for hydrogen bonded backbone and be useful for modelling cyclic pentapeptides both synthetic and bioactive in nature.

Lesbian, gay, bisexual, trans, and queer visibility through selfies: Comparing platform mediators across Ruby Rose’s Instagram and Vine presence

This article investigates the relationship between social media platforms and the production and dissemination of selfies in light of its implications for the visibility of lesbian, gay, bisexual, trans, and queer (LGBTQ) people. Applying an Actor Network Theory lens, two popular visual media apps, Instagram and Vine, are examined through a comparative walkthrough method. This reveals platform elements, or mediators, that can influence the conversational capacity of selfies in terms of the following: range, the variety of discourses addressed within a selfie; reach, circulation within and across publics; and salience, the strength and clarity of discourses communicated through a selfie. These mediators are illustrated through LGBTQ celebrity Ruby Rose’s Instagram selfies and Vine videos. Instagram’s use expectations encourage selfies focused on mainstream discourses of normative beauty and conspicuous consumption with an emphasis on appearance, extending through features constraining selfies’ reach and salience. In contrast, Vine’s broader use expectations enable a variety of discourses to be communicated across publics with an emphasis on creative, first-person sharing. These findings are reflected in Rose’s Instagram selfies, which mute alternative discourses of gender and sexuality through desexualized and aesthetically appealing self-representations, while Vines display her personal side, enabling both LGBTQ and heterosexual, cisgender people to identify with her without minimizing non-normative aspects of her gender and sexuality. These findings demonstrate the relevance of platforms in shaping selfies’ conversational capacity, as mediators can influence whether selfies feature in conversations reinforcing dominant discourses or in counterpublic conversations, contributing to everyday activism that challenges normative gender and sexual discourses.

A real-time algorithm for simulation of flexible objects and hyper-redundant manipulators

Flexible objects such as a rope or snake move in a way such that their axial length remains almost constant. To simulate the motion of such an object, one strategy is to discretize the object into large number of small rigid links connected by joints. However, the resulting discretised system is highly redundant and the joint rotations for a desired Cartesian motion of any point on the object cannot be solved uniquely. In this paper, we revisit an algorithm, based on the classical tractrix curve, to resolve the redundancy in such hyper-redundant systems. For a desired motion of the `head' of a link, the `tail' is moved along a tractrix, and recursively all links of the discretised objects are moved along different tractrix curves. The algorithm is illustrated by simulations of a moving snake, tying of knots with a rope and a solution of the inverse kinematics of a planar hyper-redundant manipulator. The simulations show that the tractrix based algorithm leads to a more `natural' motion since the motion is distributed uniformly along the entire object with the displacements diminishing from the `head' to the `tail'.

A model of the polarization position-angle swings in BL Lacertae objects

The polarization position-angle swings that have been measured in a number of BL Lacertae objects and highly variable quasars are interpreted in terms of shock waves which illuminate (by enhanced synchrotron radiation) successive transverse cross sections of a magnetized, relativistic jet. The jet is assumed to have a nonaxisymmetric magnetic field configuration of the type discussed in the companion paper on the equilibria of force-free jets. For a jet that is viewed at a small angle to the axis, the passage of a shock will give rise to an apparent rotation of the polarization position angle whose amplitude can be substantially larger than 180 deg. The effects of freely propagating shocks are compared with those of bow shocks which form in front of dense obstacles in the jet, and specific applications to 0727 - 115 and BL Lacertae are considered. In the case of 0727 - 115, it is pointed out that the nonuniformity of the swing rate and the apparent oscillations of the degree of polarization could be a consequence of relativistic aberration.

Low-lying states of transverse substituted trans-polyacetylene and trans-polyacetylene: A comparative DMRG study

The density-matrix renormalization group (DMRG) method is used for a comparative study of low-lying excitations in trans-polyacetylene (t-PA) and transversely substituted t-PA (TS-t-PA). We have employed the Pariser-Parr-Pople model Hamiltonian which incorporates long-range electronic correlations to model these systems. We find some fundamental differences in the excited states of the t-PA and TS-t-PA. We find that the lowest two-photon allowed excited state in TS-t-PA is not made up of two triplet excitons and the gap to this state is nonzero even for undimerized chains in the thermodynamic limit. Contrary to earlier results for the Hubbard model, we find that the lowest two-photon state is always below the first optically allowed state in all the systems studied here making TS-t-PA systems only weakly fluorescent materials. Nonresonant tumbling averaged linear and third harmonic generation optic coefficients of TS-t-PA systems are also much smaller than that of t-PA.