SET1, A Yeast Member of the Trithorax Family, Functions in Transcriptional Silencing and Diverse Cellular Processes

The trithorax gene family contains members implicated in the control of transcription, development, chromosome structure, and human leukemia. A feature shared by some family members, and by other proteins that function in chromatin-mediated transcriptional regulation, is the presence of a 130- to 140-amino acid motif dubbed the SET or Tromo domain. Here we present analysis of SET1, a yeast member of the trithorax gene family that was identified by sequence inspection to encode a 1080-amino acid protein with a C-terminal SET domain. In addition to its SET domain, which is 40–50% identical to those previously characterized, SET1 also shares dispersed but significant similarity to Drosophila and human trithorax homologues. To understand SET1 function(s), we created a null mutant. Mutant strains, although viable, are defective in transcriptional silencing of the silent mating-type loci and telomeres. The telomeric silencing defect is rescued not only by full-length episomal SET1 but also by the conserved SET domain of SET1. set1 mutant strains display other phenotypes including morphological abnormalities, stationary phase defects, and growth and sporulation defects. Candidate genes that may interact with SET1 include those with functions in transcription, growth, and cell cycle control. These data suggest that yeast SET1, like its SET domain counterparts in other organisms, functions in diverse biological processes including transcription and chromatin structure.

Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1

Activating mutations in the Kit receptor tyrosine kinase have been identified in both rodent and human mast cell leukemia. One activating Kit mutation substitutes a valine for aspartic acid at codon 816 (D816V) and is frequently observed in human mastocytosis. Mutation at the equivalent position in the murine c-kit gene, involving a substitution of tyrosine for aspartic acid (D814Y), has been described in the mouse mastocytoma cell line P815. We have investigated the mechanism of oncogenic activation by this mutation. Expression of this mutant Kit receptor tyrosine kinase in a mast cell line led to the selective tyrosine phosphorylation of a 130-kDa protein and the degradation, through the ubiquitin-dependent proteolytic pathway, of a 65-kDa phosphoprotein. The 65-kDa protein was identified as the src homology domain 2 (SH2)-containing protein tyrosine phosphatase SHP-1, a negative regulator of signaling by Kit and other hematopoietic receptors, and the protein product of the murine motheaten locus. This mutation also altered the sites of receptor autophosphorylation and peptide substrate selectivity. Thus, this mutation activates the oncogenic potential of Kit by a novel mechanism involving an alteration in Kit substrate recognition and the degradation of SHP-1, an attenuator of the Kit signaling pathway.

Periodic variation in side-chain polarities of T-cell antigenic peptides correlates with their structure and activity.

We present an analysis that synthesizes information on the sequence, structure, and motifs of antigenic peptides, which previously appeared to be in conflict. Fourier analysis of T-cell antigenic peptides indicates a periodic variation in amino acid polarities of 3-3.6 residues per period, suggesting an amphipathic alpha-helical structure. However, the diffraction patterns of major histocompatibility complex (MHC) molecules indicate that their ligands are in an extended non-alpha-helical conformation. We present two mutually consistent structural explanations for the source of the alpha-helical periodicity, based on an observation that the side chains of MHC-bound peptides generally partition with hydrophobic (hydrophilic) side chains pointing into (out of) the cleft. First, an analysis of haplotype-dependent peptide motifs indicates that the locations of their defining residues tend to force a period 3-4 variation in hydrophobicity along the peptide sequence, in a manner consistent with the spacing of pockets in the MHC. Second, recent crystallographic determination of the structure of a peptide bound to a class II MHC molecule reveals an extended but regularly twisted peptide with a rotation angle of about 130 degrees. We show that similar structures with rotation angles of 100-130 degrees are energetically acceptable and also span the length of the MHC cleft. These results provide a sound physical chemical and structural basis for the existence of a haplotype-independent antigenic motif which can be particularly important in limiting the search time for antigenic peptides.

Ancient Rome, Italy (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Pianta delle vestigia di Roma, secondo le osservazioni di Antonio de Romanis, ach. e socio dell' accad. di archeol. e di Antonio Nibby profess. di archeologia nell Vniv. di Roma e Socio della Stessa Accademia dallo stesso corretta ed amliata seconodo le vltime scoperte. data in lvce da Venanzio Monaldini Libraio L Anno MDCCCXXVI; Gio Acquaroni dis. e inc. It was published by presso Veanzio Monaldini ... con approvazione e privilegio Pontificio in 1826. Scale [ca. 1:8,769]. Covers area including portion of the modern city of Rome and Vatican City. The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features of Ancient Rome such as roads, drainage, selected buildings, city walls, gates, and fortifications, arches, and sepulchres. Relief is shown by hachures. Includes index, notes, and insets showing floor plans of selected historical sites.This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Rome, Italy, 1887 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of Rome 1887 : the ancient monuments, the gates, and the other important places are coloured red; the numbers correspond with those in the accompanying lists. It was published in [1887]. Scale [1:9,000]. Covers Rome, Italy and Vatican City. Map in English with Italian place names.The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map.This map shows features such as roads, railroads, drainage, built-up areas and selected buildings, walls, gates, fortification, ground cover, and more. Relief is shown by hachures. Includes indexes.This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

The History and Challenges of Cohesion Policies. Jean Monnet/Robert Schuman Paper Series Vol. 14 No. 2, February 2014

From Introduction. Regional economic disequilibria was viewed as both an obstacle to and result of integration (European Commission 1965; European Commission 1962; European Commission 1969). Even within the Treaty of Rome, the Community tried to establish mechanisms to alleviate regional inequality. However, it was not until 1975 that the main mechanism of regional policy was established as a result of British and Irish enlargement: the European Regional Development Fund (ERDF). Since then, cohesion policy has become a significant EU expenditure accounting for €347bn, or 35.7% of the total EU budget for 2007-13(European Commission Regional Policy-Info Regio 2012). It has also become a key policy linked to enlargement. The underlying principle of cohesion policy assumes that the market alone cannot solve development problems and therefore government intervention is needed. This notion is in direct contrast to the underlying principle of EU competition policy, which asserts that the free market can solve economic development problems (Meadows, interview by author, 2003). The logic underlying cohesion policy is not only counter to EU competition policy, but also regulatory policies. Unlike other EU policies, cohesion policy is not a sectoral policy, but rather territorial in nature (Leonardi, 2006). Thus at times EU regulatory policy has also unintentionally worked counter to the goals of regional policy, sometimes disadvantaging poorer regions (Dudek, 2005). As the Community has sought to ameliorate regional disparities, it meant that all levels of government: local, regional, national and supranational would need to be involved, however, member states have different territorial governance and European regional development programs have to varying degrees impacted the relationship and policy responsibility of different levels of government (Leonardi, 2006; Bachtler and Michie 1993; Marks, 1993). The very nature of regional development policy has provoked a re-examination of subsidiarity, or which level of government is the lowest and most appropriate level. The discussion of policy formulation and implementation at the lowest level possible also addresses the issue of the democratic deficit. Some argue that the closer government is to the people the more responsive and representative it is. Democracy, however, also implies that public funds are used in a transparent way and for public rather than private good. Yet, as we examine the history and current situation of EU regional funds we find that corruption and misuse still abound. Thus, to understand the history of regional policy it is imperative to look at the major transformations of the policy, how regional policy has impacted subsidiarity and the quality of democracy, become an important instrument of enlargement and contradicted or conflicted with other EU policies.

Lithogenic and biogenic daily and annual particle fluxes on the Lomonosov Ridge of trap LOMO-2

Investigations of lithogenic and biogenic particle fluxes using long-term sediment traps are still very rare in the northern high latitudes and restricted to the arctic marginal seas and sub-arctic regions. Here, for the first time, data on the variability of fluxes of lithogenic matter, carbonate, opal, and organic carbon as well as biomarker composition from the central Arctic Ocean are presented for a one-year period. The study has been carried out on material obtained from a long-term mooring system equipped with two multi-sampling-traps (150 and 1550 m water depth) and deployed on the southern Lomonosov Ridge close to the Laptev Sea continental margin from September 1995 to August 1996. In addition, data from surface-sediments were included in the study to get more information about the flux and sedimentation of organic carbon in this area. Annual fluxes of lithogenic matter, carbonate, opal, and particulate organic carbon are 3.9 g/m**2/y, 0.8 g/m**2/y, 2.6 g/m**2/y, 1.5 g/m**2/y, respectively, at the shallow trap and 11.3 g/m**2/y, 0.5 g/m**2/y, 2.9 g/m**2/y, 1.05 g/m**2/y, respectively, at the deep trap. Both the shallow as well as the deep trap show significant differences in vertical flux values over the year. Higher values were found from mid-July to end of October (total flux of 75-130 mg/m**2/d in the shallow trap and 40-225 mg/m**2/d in the deep trap, respectively). During all other months, fluxes were fairly low in both traps (most total flux values <10 mg/m**2/d1). The interval of increased fluxes can be separated into (1) a mid-July/August maximum caused by increased primary production as documented in high abundances of marine biomarkers and diatoms, and (2) a September/October (absolute) maximum caused by increased influence of Lena river discharge indicated by maximum lithogenic flux and high portions of terrigenous/fluvial biomarkers in both traps. Here, total fluxes in the deep trap were significantly higher than in the shallow trap, suggesting a lateral sediment flux at greater depth. The lithogenic flux data also support the importance of sediment input from the Laptev Sea for the sediment accumulation on the Lomonosov Ridge on geological time scales, as indicated in sedimentary records from this region.

Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: Associations with one-year neurologic outcome

THE AIM OF THE STUDY There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). METHODS We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. RESULTS Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p<0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p=0.03). During the first 48h the median (IQR) of the TW mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. CONCLUSIONS Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients.

The officer's manual. Military maxims of Napoleon.

Contains 68 maxims, annotated by M. Burnod.

Catharine of Russia ; or, The child of the storm : an historical drama, founded on an incident in the life of Peter the Great.

Separated from some unknown collection.

Empress Innocence, the life of Marie-Louise,

"First edition."

Ideals of science & faith : essays by various authors /

Introduction.--Approaches through science and education: Lodge, O., Sir. A physicists's approach. Thompson, J. A. A biological approach. Muirhead, J. H. A psychological approach. Branford, V. V. A sociological approach towards unity. Russell, B. An ethical approach. Geddes, P. An educational approach ; a technical approach.--Approaches through faith: Kelman, J. A. Presbyterian approach. Bayne, R. A Church of England approach. Waggett, P. N. The church as seen from outside. Ward, W. A. Church of Rome approach.

A catalog of the Napoleon library of De Paul university,

Mode of access: Internet.

The establishment of Maximilian's empire in Mexico.

Thesis (PH. D.)--University of Pennsylvania, 1912.

Life of Napoleon.

Atlas has imprint: New York, D. Van Nostrand.