Folding funnels and frustration in off-lattice minimalist protein landscapes

A full quantitative understanding of the protein folding problem is now becoming possible with the help of the energy landscape theory and the protein folding funnel concept. Good folding sequences have a landscape that resembles a rough funnel where the energy bias towards the native state is larger than its ruggedness. Such a landscape leads not only to fast folding and stable native conformations but, more importantly, to sequences that are robust to variations in the protein environment and to sequence mutations. In this paper, an off-lattice model of sequences that fold into a β-barrel native structure is used to describe a framework that can quantitatively distinguish good and bad folders. The two sequences analyzed have the same native structure, but one of them is minimally frustrated whereas the other one exhibits a high degree of frustration.

Interval bias in 2AFC detection tasks: sorting out the artifacts

Proportion correct in two-alternative forcedchoice (2AFC) detection tasks often varies when the stimulus is presented in the first or in the second interval.Reanalysis of published data reveals that these order effects (or interval bias) are strong and prevalent, refuting the standard difference model of signal detection theory. Order effects are commonly regarded as evidence that observers use an off-center criterion under the difference model with bias. We consider an alternative difference model with indecision whereby observers are occasionally undecided and guess with some bias toward one of the response options. Whether or not the data show order effects, the two models fit 2AFC data indistinguishably, but they yield meaningfully different estimates of sensory parameters. Under indeterminacy as to which model governs 2AFC performance, parameter estimates are suspect and potentially misleading. The indeterminacy can be circumvented by modifying the response format so that observers can express indecision when needed. Reanalysis of published data collected in this way lends support to the indecision model. We illustrate alternative approaches to fitting psychometric functions under the indecision model and discuss designs for 2AFC experiments that improve the accuracy of parameter estimates, whether or not order effects are apparent in the data.

A Minor Change?: A Case Study of Carleton Place's Integration of Minor Variance Procedures into Ontario's Development Permit System

The Development Permit System has been introduce with minimal directives for establishing a decision making process. This is in opposition to the long established process for minor variances and suggests that the Development Permit System does not necessarily incorporate all of Ontario’s fundamental planning principles. From this concept, the study aimed to identify how minor variances are incorporated into the Development Permit System. In order to examine this topic, the research was based around the following research questions: • How are ‘minor variance’ applications processed within the DPS? • To what extent do the four tests of a minor variance influence the outcomes of lower level applications in the DPS approval process? A case study approach was used for this research. The single-case design employed both qualitative and quantitative research methods including a review of academic literature, court cases, and official documents, as well as a content analysis of Class 1, 1A, and 2 Development Permit application files from the Town of Carleton Place that were decided between 2011 and 2015. Upon the completion of the content analysis, it was found that minor variance issues were most commonly assigned to Class 1 applications. Planning staff generally met approval timelines and embraced their delegated approval authority, readily attaching conditions to applications in order to mitigate off-site impacts. While staff met the regulatory requirements of the DPS, ‘minor variance’ applications were largely decided on impact alone, demonstrating that the principles established by the four tests, the defining quality of the minor variance approval process, had not transferred to the Development Permit System. Alternatively, there was some evidence that the development community has not fully adjusted to the requirements of the new approvals process, as some applications were supported using a rationale containing the four tests. Subsequently, a set of four recommendations were offered which reflect the main themes established by the findings. The first two recommendations are directed towards the Province, the third to municipalities and the fourth to developers and planning consultants: 1) Amend Ontario Regulation 608/06 so that provisions under Section 4(3)(e) fall under Section 4(2). 2) Change the rhetoric from “combining elements of minor variances” to “replacing minor variances”. 3) Establish clear evaluation criteria. 4) Understand the evaluative criteria of the municipality in which you are working.

Liberalising trade in services: creating new migration opportunities? Research Paper in Law, 1/2010

Introduction. It is quite uncommon to associate migration with the rules on services trade. Indeed, all economic definitions of services insist on their immaterial nature and on the increased possibility of trading them ‘virtually’ over networks or else, without any physical movement of the parties involved. Somehow this ‘immaterial’ nature of services reflects on their providers/recipients which seem to be ‘invisible’. Even though most services still require the physical contact of the provider with the recipient1 and, when provided over national borders, do entail migration, service providers and/or recipients are rarely thought of as ‘immigrants’. This may be due to the fact that they enter the foreign territory with a specific aim and, once this aim accomplished, move back to their state of origin; technically they only qualify as short term non-cyclical migrants and are of little interest to policy-makers. A second reason may be that both service providers and recipients are economically desirable: the former are typically highly skilled and trained professionals and the latter are well-off ‘visitors’, increasing consumption in the host state. The legal definition of services in Article 57 TFEU (ex Art. 50 EC) further nourishes this idea about service providers/recipients not being migrants: the relevant Treaty rules only apply when the provisions on free movement of workers and freedom of establishment – themselves clearly linked to migration – do not apply. This distinction has been fleshed up by the ECJ which has consistently held that the distinction between the rules on establishment, on the one hand, and the rules on services, on the other, lies on duration.2 Indeed, all EC manuals state four types of service provision falling under the EC Treaty: a) where the service provider moves to the recipient’s state, for a short period of time (longer stay would amount to establishment), b) where the service recipients themselves move to the state where the service is offered (eg for medical care, education, tourism etc), c) where both service providers and recipients move together in another member state (eg a tourist guide accompanying a group travelling abroad) and d) where the service itself is provided across the borders (typically through the use of ICTs). None of these situations would typically qualify as migration. The above ‘dissociation’ between services and migration has been gradually weakened in the recent years. Indeed, migration is increasingly connected to the transnational provision of services. This is the result of three kinds of factors: developments in the European Court of Justice’s (ECJ) case law; legislative initiatives in the EU; and the GATS. Each one of these is considered in some detail below. The aim of the analysis which follows is to show the extent to which (legislative and judicial) policies aimed at the free provision of services actively affect migration conditions within the EU. The EC rules on the provision of services primarily affect the movement of EU nationals. As it will be shown below, however, third country nationals (TCNs) may also claim the benefits of the rules on services, either as recipients thereof or as employees of some EC undertaking which is providing services in another member state (posted workers).

EU Trade Actors after Lisbon: Enhanced Negotiations or Business as Usual? Brugges Political Research Paper No. 32, November 2013

As seen by the launching of trade negotiations with Japan and the United States, the European Union has shifted gears in order to achieve amplified benefits in bilateral trade agreements. The entry into force of the Lisbon Treaty brought the European Parliament and the European External Action Service into the picture as new actors in trade negotiations. The question arises if the new framework of trade negotiations is better off than the pre-Lisbon era. By applying Veto Players theory to the Central American Association Agreement and Principal-Agent theory to the Ukrainian Association Agreement, two results were concluded. First, the participation of the European Parliament as a veto player has decreased the effectiveness of trade negotiation. Second, the participation of the European External Action Service has shown the contrary, namely an increase of effectiveness in trade negotiations.

TTIP’s Hard Core: Technical barriers to trade and standards. Paper No. 13 in the CEPS-CTR project ‘TTIP in the Balance’ and CEPS Special Report No. 117/August 2015

Michelle Egan and Jacques Pelkmans provide an overview of the TBT chapter in TTIP and the various issues between the US and the EU in this area, which in turn requires extensive expositions of domestic regulation in the US and the EU. TBTs, outside heavily regulated sectors such as chemicals, automobiles or medicines (which have separate chapters in TTIP), can be caused by divergent (voluntary) standards, technical regulations and conformity assessment. Indeed, in all three the US and the EU have long experienced frictions with considerable trading costs. The 1998 Mutual Recognition Agreement about conformity assessment only succeeded in two out of six sectors. The US and European standardisation traditions differ and this paper explains why it is so hard, also economically, to realise convergence. However, the authors reject the unproductive ‘stand-off’ between US and EU negotiators on standardisation and suggest to clarify the enormous economic ‘installed base’ of prominent US standards in the world economy and build a solution from there. As to technical regulation, the prospect of converging regulation (via harmonisation) is often dim, but equivalence (given similar levels of regulatory protection) can be an option.

A new institutional approach to Japanese firms' foreign direct investment under free trade agreements

This paper examines the determinants of foreign direct investment (FDI) under free trade agreements (FTAs) from a new institutional perspective. First, the determinants of FDI are theoretically discussed from a new institutional perspective. Then, FDI is statistically analyzed at the aggregate level. Kernel density estimation of firm-size reveals some evidence of "structural changes" after FTAs, as characterized by the investing firms' paid-up capital stock. Statistical tests of the average and variance of the size distribution confirm this in the case of FTAs with Asian partner countries. For FTAs with South American partner countries, the presence of FTAs seems to promote larger-scale FDIs. These results remain correlational instead of causal, and more statistical analyses would be needed to infer causality. Policy implications suggest that participants should consider "institutional" aspects of FTAs, that is, the size matters as a determinant of FDI. Future work along this line is needed to study "firm heterogeneity."

Sedimentology and stable isotope ratios of planktonic foraminifera from two cores off Northeastern Brazil

The stable isotope composition of planktonic foraminifera correlates with evidence for pulses of terrigenous sediment in a sediment core from the upper continental slope off northeastern Brazil. Stable oxygen isotope records of the planktonic foraminiferal species Globigerinoides sacculifer and Globigerinoides ruber (pink) reveal sub-Milankovitch changes in sea-surface hydrography during the last 85,000 yr. Warming of the surface water coincided with terrigenous sedimentation pulses that are inferred from high XRF intensities of Ti and Fe, and which suggest humid conditions in northeast Brazil. These tropical signals correlate with climatic oscillations recorded in Greenland ice cores (Dansgaard-Oeschger cycles) and in sediment cores from the North Atlantic (Heinrich events). Trade winds may have caused changes in the North Brazil Current that altered heat and salt flux into the North Atlantic, thus affecting the growth and decay of the large glacial ice sheets.

Sea surface temperatures derived from alkenones from Late Quaternary sediments of the East Equatorial South Atlantic

Angola Basin and Walvis Ridge records of past sea surface temperatures (SST) derived from the alkenone Uk 37 index are used to reconstruct the surface circulation in the east equatorial South Atlantic for the last 200,000 years. Comparison of SST estimates from surface sediments between 5° and 20°S with modern SST data suggests that the alkenone temperatures represent annual mean values of the surface mixed layer. Alkenone-derived temperatures for the warm climatic maxima of the Holocene and the penultimate interglacial are 1 to 4°C higher than latest Holocene values. All records show glacial to interglacial differences of about 3.5°C in annual mean SST, which is about 1.5°C greater than the difference estimated by CLIMAP (1981) for the eastern Angola Basin. At the Walvis Ridge, significant SST variance is observed at all of the Earth's orbital periodicities. SST records from the Angola Basin vary predominantly at 23- and 100-kyr periodicities. For the precessional cycle, SST changes at the Walvis Ridge correspond to variations of boreal summer insolation over Africa and lead ice volume changes, suggesting that the east equatorial South Atlantic is sensitive to African monsoon intensity via trade-wind zonality. Angola Basin SST records lag those from the Walvis Ridge and the equatorial Atlantic by about 3 kyr. The comparison of Angola Basin and Walvis Ridge SST records implies that the Angola-Benguela Front (ABF) (currently at about 14-16°S) has remained fairly stationary between 12° and 20°S (the limits of our cores) during the last two glacial-interglacial cycles. The temperature contrast associated with the ABF exhibits a periodic 23-kyr variability which is coherent with changes in boreal summer insolation over Africa. These observations suggest that surface waters north of the present ABF have not directly responded to monsoon-modulated changes in the trade-wind vector, that the central field of zonally directed trades in the southern hemisphere was not shifted or extended northward by several degrees of latitude during glacials, and that a cyclonic gyre circulation has existed in the east equatorial South Atlantic over the last 200,000 years. This scenario contradicts former assumptions of glacial intensification of the Benguela Current into the eastern Angola Basin and increased coastal upwelling off Angola.

Pollen abundance in Late Quaternary sediment cores off West Africa

The pollen record of three marine late Quaternary cores off Senegal shows a juxtaposition of Mediterranean, Northern Saharan, Central Saharan elements, which are considered transported by the trade winds from a winter-rainfall area, and Sahelian, Soudanese, Soudano-Guinean elements, considered transported both by winds and mostly by the Senegal River, and coming from the monsoonal, summer tropical rainfall area of southern West Africa. Littoral vegetation is either the edaphically dry and saline Chenopodiaceae from sebkhas at the time of the main regression, or the warm tropical humid mangrove with Rhizophora during the humid optimum period. Four stratigraphic zones reflect, from basis to top: Zone 4. A semi-arid period with a balanced pollen input. Zone 3. A very arid period with the disappearance of monsoonal pollen, probably from the disappearance of the Senegal River, a very saline littoral plain with Chenopodiaceae, a larger input of northern Saharan pollen from intensified trade winds. Zone 2. A quite humid period, much more so than today, very suddenly established, with a northward extension of the monsoonal areas, a rich littoral mangrove, and weakening of the trade winds. Zone l. A slow and steady evolution toward the present semi-humid conditions with regression of the mangrove, and of the monsoonal areas toward the south. Tentative datations and correlations with the Tchad area suggested: zone 4: 22,500 to 19,000 years BP; zone 3: 19,000 to 12,500 years BP; zone 2: 12,500 to 5,500 years BP; zone 1: 5,500 years BP to top of core. Dinoflagellate cysts display a tropical assemblage with mostly estuarine neritic elements and also a weak oceanic component, mostly in the lower slope core 47. Cosmopolitan taxa dominate the assemblage and only a few species point to more specialized environments. Quantitative variations of the assemblage are the basis of stratigraphy which is not similar to the pollen stratigraphy, and an inshore-outshore gradient has to be taken into account to correlate the three cores.

The late Pliocene pollen record of ODP Site 108-658 off Cape Blanc, Atlantic Ocean

A 200 m long marine pollen record from ODP Site 658 (21°N, 19°W) reveals cyclic fluctuations in vegetation and continental climate in northwestern Africa from 3.7 to 1.7 Ma. These cycles parallel oxygen isotope stages. Prior to 3.5 Ma, the distribution of tropical forests and mangrove swamps reached Cape Blanc, 5°N of the present distribution. Between 3.5 and 2.6 Ma, forests occurred at this latitude during irregular intervals and nearly disappeared afterwards. Likewise, a Saharan paleoriver flowed continuously until isotope Stage 134 (3.35 Ma). When river discharge ceased, wind transport of pollen grains prevailed over fluvial transport. Pollen indicators of trade winds gradually increased between 3.3 and 2.5 Ma. A strong aridification of the climate of northwestern Africa occurred during isotope Stage 130 (3.26 Ma). Afterwards, humid conditions reestablised followed by another aridification around 2.7 Ma. Repetitive latitudinal shifts of vegetation zones ranging from wooded savanna to desert flora dominated for the first time between between 2.6 and 2.4 Ma as a response to the glacial stages 104, 100 and 98. Although climatic conditions, recorded in the Pliocene, were not as dry as those of the middle and Late Pleistocene, latitudinal vegetation shifts near the end of the Pliocene resembled those of the interglacial-glacial cycles of the Brunhes chron.

Changes in the vegetation and trade winds in equatorial Northwest Africa 140,000-70,000 yr B.P., as deduced from two marine pollen records

The deep-sea cores M 16415-2 and M 16416-2 at about 9°N off Sierra Leone were analysed palynologically for the time interval 140,000-70,000 yr B.P. Results were presented in absolute (pollen concentration and pollen influx) and relative diagrams (pollen percentage). In a previous study it was evidenced that in northwest Africa pollen is mainly transported to the Atlantic by wind, so that the efficiency of aeolian pollen transport (pollen flux) could be used to evaluate changes in the intensity of the northeast trade winds. The glacial episodes (represented by the oxygen isotope stages 6 and 4) are characterized by strong northeast trade winds, whereas the last interglacial (stage 5) is characterized by weak trade winds. The pollen influx diagram shows that the intensity of the trade winds increased slightly during the relatively cool intervals of stage 5 (viz. 5.4 and 5.2). Tropical forest had maximally expanded around 124,000 yr B.P. (stage 5.5), around 98,000 yr B.P. (transition of stage 5.3 to 5.2), and around 70,000 yr B.P. (first part of stage 4): an increasing delay of the response of tropical forest to global intervals with maximum temperature is apparent during the last interglacial. As tropical forests need continuous humidity, the record of tropical forest monitors changes in climatic humidity south of the Sahara. During the last interglacial, the southern boundary of the Sahara shifted only little: expansions and contractions of the tropical forest area are correlated with contra-oscillations of the grass-dominated savanna zone. Great latitudinal shifts of the desert savanna boundary, on the contrary, occurred during the penultimate glacial interglacial transition (around 128,000 yr B.P.) to the north, and during the last interglacial-glacial transition (around 65,000 yr B.P.) to the south.

Benthic foraminifera off West Africa (1°N to 32°S)

Recent benthic foraminifera (> 125 µm) were investigated from multicorer samples on a latitudinal transect of 20 stations between 1°N and 32°S along the upper slope off West Africa. Samples were selected from a narrow water depth interval, between 1200 and 1500 m, so that changes in water masses are minimized, but changes in surface productivity are important and the only significant environmental variable. Live (Rose Bengal stained) benthic foraminifera were counted from the surface sediment down to a maximum of 12 cm. Dead foraminifera were investigated in the top 5 cm of the sediment only. Five live and five dead benthic foraminiferal assemblages were identified using Q-mode principal component analysis, matching distinct primary productivity provinces, characterized by different systems of seasonal and permanent upwelling. Differences in seasonality, quantity, and quality of food supply are the main controlling parameters on species composition and distribution of the benthic foraminiferal faunas. To test the sensitivity of foraminiferal studies based on the uppermost centimeter of sediment only, a comparative Q-mode principal component analysis was conducted on live and dead foraminiferal data from the top 1 cm of sediment. It has been demonstrated that, on the upper slope off West Africa, most of the environmental signals as recorded by species composition and distribution of the 'total' live and dead assemblages, i.e., including live and dead foraminifera from the surface sediment down to 12 cm and 5 cm, respectively, can be extracted from the assemblages in the top centimeter of sediment only. On the contrary, subsurface abundance maxima of live foraminifera and dissolution of empty tests strongly bias quantitative approaches based on the calculation of standing stocks and foraminiferal numbers in the topmost centimeter.

Geochemistry of sediments from the upwelling off Morocco

The high-productive upwelling area off Morocco is part of one of the four major trade-wind driven continental margin upwelling zones in the world oceans. While coastal upwelling occurs mostly on the shelf, biogenic particles derived from upwelling are deposited mostly at the upper continental slope. Nutrient-rich coastal water is transported within the Cape Ghir filament region at 30°N up to several hundreds of kilometers offshore. Both upwelling intensity and filament activity are dependent on the strength of the summer Trades. This study is aimed to reconstruct changes in trade wind intensity over the last 250,000 years by the analysis of the productivity signal contained in the sedimentary biogenic particles of the continental slope and beneath the Cape Ghir filament. Detailed geochemical and geophysical analyses (TOC, carbonate, C/N, delta13Corg, delta15N, delta13C of benthic foraminifera, delta18O of benthic and planktic foraminifera, magnetic susceptibility) have been carried out at two sites on the upper continental slope and one site located further offshore influenced by the Cape Ghir filament. A second offshore site south of the filament was analyzed (TOC, magnetic susceptibility) to distinguish the productivity signal related to the filament signal from the general offshore variability. Higher productivity during glacial times was observed at all four sites. However, the variability of productivity during glacial times was remarkably different at the filament-influenced site compared to the upwelling-influenced continental slope sites. In addition to climate-related changes in upwelling intensity, zonal shifts of the upwelling area due to sea-level changes have impacted the sedimentary productivity record, especially at the continental slope sites. By comparison with other proxies related to the strength and direction of the prevailing winds (Si/Al ratio as grain-size indicator, pollen) the productivity record at the filament-influenced site reflects mainly changes in trade-wind intensity. Our reconstruction reveals that especially during glacial times trade-wind intensity was increased and showed a strong variability with frequencies related to precession.

Trade with Cuba. Hearings before the Committee on Interstate and Foreign Commerce, House of Representatives, Eighty-seventh Congress, first session, on H. R. 8465, a bill to prohibit the shipment in interstate or foreign commerce of articles imported into the United States from Cuba, and for other purposes (and identical bills); H.R. 8866, a bill tp prohibit the shipment in interstate or foreign commerce of articles imported into the United States from Cuba, to provide penalties for such shipment, and for other purposes. August 29 and September 1, 1961.

Mode of access: Internet.