An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor.

We have previously identified tyrosine-537 as a constitutively phosphorylated site on the human estrogen receptor (hER). A 12-amino acid phosphotyrosyl peptide containing a selected sequence surrounding tyrosine-537 was used to investigate the function of phosphotyrosine-537. The phosphotyrosyl peptide completely blocked the binding of the hER to an estrogen response element (ERE) in a gel mobility shift assay. Neither the nonphosphorylated tyrosyl peptide nor an unrelated phosphotyrosyl peptide previously shown to inhibit the signal transducers and activators of transcription factor (STAT) blocked binding of the hER to the ERE. The hER phosphotyrosyl peptide was shown by molecular sizing chromatography to dissociate the hER dimer into monomers. The hER specifically bound the 32P-labeled phosphotyrosyl peptide, indicating that the inhibition of ERE binding was caused by the phosphotyrosyl peptide binding directly to the hER and blocking dimerization. These data suggest that the phosphorylation of tyrosine-537 is a necessary step for the formation of the hER dimer. In addition, we propose that the dimerization of the hER occurs by a previously unrecognized Src homology 2 domain (SH2)-like phosphotyrosyl coupling mechanism. Consequently, the phosphotyrosyl peptide represents a class of antagonists that inhibits estrogen action by a mechanism other than interacting with the receptor's hormone binding site.

Mos overexpression in Swiss 3T3 cells induces meiotic-like alterations of the mitotic spindle.

High levels of mos protooncogene product are expressed during oocyte meiotic maturation and Mos has been implicated in formation of the spindle and spindle pole. Here, we show that in Swiss 3T3 cells with 4N DNA content, high levels of Mos lead to the production of binucleated cells. The Swiss 3T3 cells in mitosis, before binucleation occurs, are anastral and the spindle poles are juxtaposed to the cell membrane. These phenotypes may be related to the meiotic process of attachment of the spindle pole to the oocyte membrane during polar body formation. The production of binucleated somatic cells could result from attachment of the altered mitotic spindle pole to the cell membrane that interferes with cytokinesis but not karyokinesis. This can explain at least one form of genetic instability that leads to altered DNA content in tumor cells.

Synthesis of Chromen[4,3-b]pyrrolidines by Intramolecular 1,3-Dipolar Cycloadditions of Azomethine Ylides: An Experimental and Computational Assessment of the Origin of Stereocontrol

Azomethine ylides, generated from imine-derived O-cinnamyl or O-crotonyl salicylaldeyde and α-amino acids, undergo intramolecular 1,3-dipolar cycloaddition, leading to chromene[4,3-b]pyrrolidines. Two reaction conditions are used: (a) microwave-assisted heating (200 W, 185 °C) of a neat mixture of reagents, and (b) conventional heating (170 °C) in PEG-400 as solvent. In both cases, a mixture of two epimers at the α-position of the nitrogen atom in the pyrrolidine nucleus was formed through the less energetic endo-approach (B/C ring fusion). In many cases, the formation of the stereoisomer bearing a trans-arrangement into the B/C ring fusion was observed in high proportions. Comprehensive computational and kinetic simulation studies are detailed. An analysis of the stability of transient 1,3-dipoles, followed by an assessment of the intramolecular pathways and kinetics are also reported.

The Common Agricultural Policy: The Future of the CAP and why real reform will never happen. EUMA Paper Vol. 6 No. 7, May 2010

This paper sets out to examine the Common Agricultural Policy (CAP) of the European Union from its inception to present day 1. Specifically, this paper seeks to answer the following questions: (1) What long-term effects, if any, did the circumstances surrounding, and leading up to the formation of the CAP have; (2) What have internal and external responses been to the CAP; (3) How has the CAP responded to major events both internally (within the European Union), and externally (internationally); (4) What affect does the recently implemented Lisbon Treaty2 have on the CAP, and (5) What is the future of the CAP and CAP reform? In order to answer these questions this paper begins with the contention that the CAP is in fact the largest and strongest driving force of EU expansion. In support of this proposition, this paper first examines the circumstances and events leading to the creation of the CAP in the European Community. Second, this paper examines what long-term effects the circumstances surrounding the CAP’s inception have had on the policy, particularly calling attention to the disproportionate Franco-German CAP benefits. Third, the paper then examines how the CAP has responded to historical events that have had significant effects on the European community, particularly EU expansion, the implementation of the Lisbon Treaty, and the recent worldwide economic crisis. Finally, this paper examines common criticisms of and conflicts surrounding the CAP, both internally and externally, and argues that CAP reform, at least within the current institutional framework of the European Union, can never truly occur.

Eurasian integration. Russia's attempt at the economic unification of the post-Soviet area. OSW Study 44/2013

In 2009, Vladimir Putin, the then Russian prime minister, gave impetus to the establishment of closer relations within what was then a still narrow group of three countries: Russia, Kazakhstan and Belarus. Russia was determined in embarking on the implementation of the principles of the Customs Union among these three states and, since 2012, within the Common Economic Space as well. This process of integration is intended to bring about the introduction of ‘four freedoms’ in this area: the free movement of goods, services, capital and labour. From Moscow’s point of view, building up such integration structures is especially necessary in order to counteract the economic expansion of the European Union and China. It also feels it is important to take measures against the loosening of the bonds between the CIS countries and Russia. At the same time, close co-operation is expected to guarantee for Russia that the strong politico-economic influences in this area will be maintained. Despite the numerous limitations of the integration process, such as the small number of the participating states or limited progress in implementing the CES, this is still the most advanced integration programme in the region seen since the collapse of the USSR. Progress in putting the rules of the Customs Union into practice can be seen as a success for Moscow. In turn, the formation of the CES is still at an early stage, and it is difficult to determine at this point to what extent the three countries will harmonise their markets.

Tectonic evolution of the Proterozoic Itremo Group metasediments in central Madagascar

The major geologic units of the Itremo region in central Madagascar include: (1) upper amphibolite to granulite facies (higher grade) Precambrian rocks, mainly para- and orthogneisses, and migmatites; (2) the newly defined Itremo Nappes, a fold-and-thrust belt containing the Proterozoic Itremo Group sediments, metamorphosed at greenschist to lower amphibolite facies (lower grade) conditions: (3) Middle Neoproterozoic and Late Neoproterozoic-Cambrian intrusives. The stratigraphic succession of the Itremo Group in the eastern part of the Itremo region is, from bottom to top: quartzites, metapelites, metacarbonates and metapelites overlain by metacarbonates. During D1 the Itremo Group sediments were detached from their continental substratum, deformed into a fold-and-thrust nappe (Itremo Nappes), and transported on top of higher grade rocks that are intruded by Middle Neoproterozoic (c. 797–780 Ma) granites and gabbros. A second phase of deformation shortening (D2) affected both the Itremo Sedimentary Nappes and structurally underlying higher-grade rocksunits, and formed large-scale N-S-trending F2 folds. S1 axial plane foliations in Itremo Group sediments are truncated by Late Neoproterozoic-Cambrian granites (c. 570–540 Ma). The age of the formation of the Itremo Nappes is not well constrained: they formed in Neoproterozoic times between 780 and 570 Ma.

Sedimentology at the continental margin of the southern Weddell Sea

During four expeditions with RV "Polarstern" at the continental margin of the southern Weddell Sea, profiling and geological sampling were carried out. A detailed bathymetric map was constructed from echo-sounding data. Sub-bottom profiles, classified into nine echotypes, have been mapped and interpreted. Sedimentological analyses were carried out on 32 undisturbed box grab surface samples, as well as on sediment cores from 9 sites. Apart from the description of the sediments and the investigation of sedimentary structures on X-radiographs the following characteristics were determined: grain-size distributions; carbonate and Corg content; component distibutions in different grain-size fractions; stable oxygen and carbon isotopes in planktic and, partly, in benthic foraminifers; and physical properties. The stratigraphy is based On 14C-dating, oxygen isotope Stages and, at one site, On paleomagnetic measurements and 230Th-analyses The sediments represent the period of deposition from the last glacial maximum until recent time. They are composed predominantly of terrigenous components. The formation of the sediments was controlled by glaciological, hydrographical and gravitational processes. Variations in the sea-ice coverage influenced biogenic production. The ice sheet and icebergs were important media for sediment transport; their grounding caused compaction and erosion of glacial marine sediments on the outer continental shelf. The circulation and the physical and chemical properties of the water masses controlled the transport of fine-grained material, biogenic production and its preservation. Gravitational transport processes were the inain mode of sediment movements on the continental slope. The continental ice sheet advanced to the shelf edge and grounded On the sea-floor, presumably later than 31,000 y.B.P. This ice movement was linked with erosion of shelf sediments and a very high sediment supply to the upper continental slope from the adiacent southern shelf. The erosional surface On the shelf is documented in the sub-bottom profiles as a regular, acoustically hard reflector. Dense sea-ice coverage above the lower and middle continental slope resulted in the almost total breakdown of biogenic production. Immediately in front of the ice sheet, above the upper continental slope, a <50 km broad coastal polynya existed at least periodically. Biogenic production was much higher in this polynya than elsewhere. Intense sea-ice formation in the polynya probably led to the development of a high salinity and, consequently, dense water mass, which flowed as a stream near bottom across the continental slope into the deep sea, possibly contributing to bottom water formation. The current velocities of this water mass presumably had seasonal variations. The near-bottom flow of the dense water mass, in combination with the gravity transport processes that arose from the high rates of sediment accumulation, probably led to erosion that progressed laterally from east to West along a SW to NE-trending, 200 to 400 m high morphological step at the continental slope. During the period 14,000 to 13,000 y.B.P., during the postglacial temperature and sea-level rise, intense changes in the environmental conditions occured. Primarily, the ice masses on the outer continental shelf started to float. Intense calving processes resulted in a rapid retreat of the ice edge to the south. A consequence of this retreat was, that the source area of the ice-rafted debris changed from the adjacent southern shelf to the eastern Weddell Sea. As the ice retreated, the gravitational transport processes On the continental slope ceased. Soon after the beginning of the ice retreat, the sea-ice coverage in the whole research area decreased. Simultaneously, the formation of the high salinity dense bottom water ceased, and the sediment composition at the continental slope then became influenced by the water masses of the Weddell Gyre. The formation of very cold Ice Shelf Water (ISW) started beneath the southward retreating Filchner-Ronne Ice Shelf somewhat later than 12,000 y.B.P. The ISW streamed primarily with lower velocities than those of today across the continental slope, and was conducted along the erosional step on the slope into the deep sea. At 7,500 y.B.P., the grounding line of the ice masses had retreated > 400 km to the south. A progressive retreat by additional 200 to 300 km probably led to the development of an Open water column beneath the ice south of Berkner Island at about 4,000 y.B.P. This in turn may have led to an additional ISW, which had formed beneath the Ronne Ice Shelf, to flow towards the Filcher Ice Shelf. As a result, increased flow of ISW took place over the continental margin, possibly enabling the ISW to spill over the erosional step On the upper continental slope towards the West. Since that time, there is no longer any documentation of the ISW in the sedimentary Parameters on the lower continental slope. There, recent sediments reflect the lower water masses of the Weddell Gyre. The sea-ice coverage in early Holocene time was again so dense that biogenic production was significantly restricted.

(Table 19, page 199) Minor constituents of one of the San Clemente iron concretions and its metallic core

The chemical and mineralogical composition of pelagic sediments from the East Pacific Ocean has been determined with the aim of defining the ultimate sources and the mechanisms of formation of the solid phases. The distribution of elements between sea-water, the pore solution and the various solid components of the sediments permits interpretations of the variations in time and space of the gross chemical composition of pelagic clays. For example, manganese, present in sea-water in a divalent form, is apparently oxidized at the sediment-water interface to tetravalent species which subsequently become a part of the group of ferromanganese oxide minerals which are found in the marine environment. It is suggested the rate of manganese accumulation in sediments is some function of the length of time the sediment surface is in contact with sea-water. The contribution of chemical species from the different geospheres is considered. The quantitative importance of pelagic clays in the major sedimentary cycle is studied on the basis of the distribution of the weathered igneous rock products between continental and pelagic deposits and sea-water. These analyses of a wide variety of pelagic clays allow a reformulation of the geochemical balance and it is concluded that pelagic clays account for approximately 13 per cent of the total mass of sediments produced over geologic time.

(Table 1) Mean sizes of Hydrobia ulvae juveniles in the littoral zone of the Chernaya Inlet (Kandalaksha Bay, White Sea) in July-September 1995

Based on observations and experiments carried out within the White Sea silty-sandy littoral zone in 1994-1997 data on biology of development and behavior of Hydrobia ulvae juveniles over water column and in sediments were obtained. Hydrobiid juveniles 0.125-0.150 mm in size appear in plankton during the second half of June and in two to three weeks they precipitate on sediments reaching 0.300-0.350 mm in size. Specific biological features of the White Sea hydrobiids are a short reproductive period and a short period of juvenile growth related to long under-ice time and decelerated warming of shallow waters. Distribution of juvenile individuals of H. ulvae is primarily determined by hydrodynamics and microtopography of the littoral zone. Redistribution of the juveniles permanently takes place, since all size groups of the juveniles are equally subjected to migration. During the first few weeks after settling mortality of juvenile mudsnails is 85%.

Petrographical investigation of the Salt Wash sediments : final report /

This report represents an attempt to use quantitative petrography to elucidate criteria for differentiating ore-bearing from barren sediments in the Salt Wash member of the Morrison formation of the Colorado Plateau. The main premise upon which this approach is based is that the factors which determine whether a sediment contains ore or not is a function largely, if not solely, of the characteristics of the sedimentary rock. It follows that if this premise is true, then the petrographic characteristics of a sediment containing ore should differ from those of the sediments which are barren.

The illustrated comprehensive history of the great battle of Shiloh,

"The formation of the National Association of Battle of Shiloh Survivors", with constitution, and an account of the first to sixteenth annual reunion: p. 181-257, 266-317.

Uranium reconnaissance of the Black Mountain-Yale Point area, Black Mesa, Navajo Indian Reservation, Arizona /

A reconnaissance for uranium was conducted in the Black Mountain-Yale Point area of Black Mesa, Arizona, from February to November 1954. Numerous uranium deposits were examined, which appear to be situated in areas of greater tectonic deformation and confined to a single stratigraphic zone in the Toreva formation of the Upper Cretaceous Mesaverde group. Locally the uranium appears to occur in the vicinity of carbonized plant material in quartzose sand lenses, within paleostream channel deposits.

Pharmacopoeia of the United States of America, The United States pharmacopoeia.

Two conventions were held in 1830, both of which issued a revision of Pharmacoepeia.