The "DEAD box" protein DbpA interacts specifically with the peptidyltransferase center in 23S rRNA.

The Escherichia coli DEAD (Asp-Glu-Ala-Asp) box protein DbpA is a putative RNA helicase and established RNA-dependent ATPase and is the only member of the DEAD box protein family for which a specific RNA substrate, bacterial 23S rRNA, has been identified. We have investigated the nature of this specificity in depth and have localized by deletion mutagenesis and PCR a single region of 93 bases (bases 2496-2588) in 23S rRNA that is both necessary and sufficient for complete activation of ATPase activity of DbpA. This target region forms part of the peptidyltransferase center and includes many bases involved in interaction with the 3' terminal adenosines of both A- and P-site tRNAs. Deletion of stem loops within the 93-base segment abolished ATPase activation. Similarly, point mutations that disrupt base pairing within stem structures ablated stimulation of ATPase activity. These data are consistent with roles for DbpA either in establishing and/or maintaining the correct three-dimensional structure of the peptidyltransferase center in 23S rRNA during ribosome assembly or in the peptidyltransferase reaction.

Shared functions in vivo of a glycosyl-phosphatidylinositol-linked aspartyl protease, Mkc7, and the proprotein processing protease Kex2 in yeast.

The MKC7 gene was isolated as a multicopy suppressor of the cold-sensitive growth phenotype of a yeast kex2 mutant, which lacks the protease that cleaves pro-alpha-factor and other secretory proproteins at pairs of basic residues in a late Golgi compartment in yeast. MKC7 encodes an aspartyl protease most closely related to product of the YAP3 gene, a previously isolated multicopy suppressor of the pro-alpha-factor processing defect of a kex2 null. Multicopy MKC7 suppressed the alpha-specific mating defect of a kex2 null as well as multicopy YAP3 did, but multicopy YAP3 was a relatively weak suppressor of kex2 cold sensitivity. Overexpression of MKC7 resulted in production of a membrane-associated proteolytic activity that cleaved an internally quenched fluorogenic peptide substrate on the carboxyl side of a Lys-Arg site. Treatment with phosphatidylinositol-specific phospholipase C shifted Mkc7 activity from the detergent to the aqueous phase in a Triton X-114 phase separation, indicating that membrane attachment of Mkc7 is mediated by a glycosyl-phosphatidylinositol anchor. Although disruption of MKC7 or YAP3 alone resulted in no observable phenotype, mkc7 yap3 double disruptants exhibited impaired growth at 37 degrees C. Disruption of MKC7 and YAP3 in a kex2 null mutant resulted in profound temperature sensitivity and more generalized cold sensitivity. The synergism of mkc7, yap3, and kex2 null mutations argues that Mkc7 and Yap3 are authentic processing enzymes whose functions overlap those of Kex2 in vivo.

Fluorescence energy transfer dye-labeled primers for DNA sequencing and analysis.

Fluorescent dye-labeled DNA primers have been developed that exploit fluorescence energy transfer (ET) to optimize the absorption and emission properties of the label. These primers carry a fluorescein derivative at the 5' end as a common donor and other fluorescein and rhodamine derivatives attached to a modified thymidine residue within the primer sequence as acceptors. Adjustment of the donor-acceptor spacing through the placement of the modified thymidine in the primer sequence allowed generation of four primers, all having strong absorption at a common excitation wavelength (488 nm) and fluorescence emission maxima of 525, 555, 580, and 605 nm. The ET efficiency of these primers ranges from 65% to 97%, and they exhibit similar electrophoretic mobilities by gel electrophoresis. With argon-ion laser excitation, the fluorescence of the ET primers and of the DNA sequencing fragments generated with ET primers is 2- to 6-fold greater than that of the corresponding primers or fragments labeled with single dyes. The higher fluorescence intensity of the ET primers allows DNA sequencing with one-fourth of the DNA template typically required when using T7 DNA polymerase. With single-stranded M13mp18 DNA as the template, a typical sequencing reaction with ET primers on a commercial sequencer provided DNA sequences with 99.8% accuracy in the first 500 bases. ET primers should be generally useful in the development of other multiplex DNA sequencing and analysis methods.

Record of cases, 1738-1758

Contains summaries of cases brought before the court of appeals with the judgment rendered by Edward Trelawny and transcribed by Samuel Williams.

Quitclaim, 1745/6 February 11

Handwritten quitclaim by Benjamin Fuller and Hannah Fuller as beneficiaries of the estate of Benjamin Wadsworth, acknowledging payment by Andrew Bordman.

Boston, Massachusetts, 1826 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of Boston comprising a part of Charlestown and Cambridgeport, engraved & published by Annin & Smith & J.V.N. Throop from actual survey ; with corrections by S.P. Fuller, surveyor. It was published in 1826. Scale [ca. 1:6,090]. Covers Boston proper (Shawmut Peninsula and Boston Neck) with small portions of Charlestown, Cambridge, and South Boston. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). 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, or other information associated with the principal map. This map shows features such as roads, proposed roads, wharves, drainage, churches, schools, selected public buildings, parks, cemeteries, city ward boundaries and more. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Boston, Massachusetts, 1846 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of Boston comprising a part of Charlestown and Cambridge, published by George G. Smith, engraver, 1846. Scale [ca. 1:7,310]. Covers Boston proper (Shawmut Peninsula and Boston Neck) with small portions of Charlestown, Cambridge, and South Boston. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). 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, or other information associated with the principal map. This map shows features such as roads, railroads, wharves, drainage, churches, schools, selected public buildings, parks, cemeteries, city ward boundaries and more. Relief is shown by hachures. Includes insets: Plan of South Boston from a drawing by S.P. Fuller. Scale [ca. 1:17,600] -- Plan of East Boston from actual survey by R.H. Eddy. Scale [ca. 1:17,000]. Includes also indexes to points of interest and streets. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Boston, Massachusetts, 1851 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of Boston comprising a part of Charlestown and Cambridge, published by George G. Smith, engraver, 1851. Scale [ca. 1:7,380]. Covers Boston proper (Shawmut Peninsula and Boston Neck) with small portions of Charlestown, Cambridge, and South Boston. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). 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, or other information associated with the principal map. This map shows features such as roads, railroads, signal stations, wharves, drainage, churches, schools, selected public buildings, parks, cemeteries, city ward boundaries and more. Relief is shown by hachures. Includes insets: Plan of South Boston from a drawing by S.P. Fuller. Scale [ca. 1:17,600] -- Plan of East Boston from actual survey by R.H. Eddy. Scale [ca. 1:17,000]. Includes also indexes to points of interest and streets. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Boston, Massachusetts, 1835 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of Boston comprising a part of Charlestown and Cambridge, published by George G. Smith, engraver, 1835. Scale [ca. 1:7,310]. Covers Boston proper (Shawmut Peninsula and Boston Neck) with small portions of Charlestown, Cambridge, and South Boston. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). 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, or other information associated with the principal map. This map shows features such as roads, railroads, wharves, drainage, churches, schools, selected public buildings, parks, cemeteries, city ward boundaries and more. Relief is shown by hachures. Includes insets: Plan of South Boston from a drawing by S.P. Fuller. Scale [ca. 1:17,600] -- Plan of East Boston from actual survey by R.H. Eddy. Scale [ca. 1:17,000]. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

CONSTITUTIONAL JUSTICE IN AFRICA: An Examination of Constitutional Positivism, Fundamental Law and Rights in Ghana and Nigeria

This work explores the idea of constitutional justice in Africa with a focus on constitutional interpretation in Ghana and Nigeria. The objective is to develop a theory of constitutional interpretation based upon a conception of law that allows the existing constitutions of Ghana and Nigeria to be construed by the courts as law in a manner that best serves the collective wellbeing of the people. The project involves an examination of both legal theory and substantive constitutional law. The theoretical argument will be applied to show how a proper understanding of the ideals of the rule of law and constitutionalism in Ghana and Nigeria necessitate the conclusion that socio-economic rights in those countries are constitutionally protected and judicially enforceable. The thesis argues that this conclusion follows from a general claim that constitutions should represent a ‘fundamental law’ and must be construed as an aspirational moral ideal for the common good of the people. The argument is essentially about the inherent character of ‘legality’ or the ‘rule of law.’ It weaves together ideas developed by Lon Fuller, Ronald Dworkin, T.R.S. Allan and David Dyzenhaus, as well as the strand of common law constitutionalism associated with Sir Edward Coke, to develop a moral sense of ‘law’ that transcends the confines of positive or explicit law while remaining inherently ‘legal’ as opposed to purely moral or political. What emerges is an unwritten fundamental law of reason located between pure morality or natural law on the one hand and strict, explicit, or positive law on the other. It is argued that this fundamental law is, or should be, the basis of constitutional interpretation, especially in transitional democracies like Ghana and Nigeria, and that it grounds constitutional protection for socio-economic rights. Equipped with this theory of law, courts in developing African countries like Ghana and Nigeria will be in a better position to contribute towards developing a real sense of constitutional justice for Africa.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.