Repression of TFII-I-dependent transcription by nuclear exclusion

TFII-I is an unusual transcription factor possessing both basal and signal-induced transcriptional functions. Here we report the characterization of a TFII-I-related factor (MusTRD1/BEN) that regulates transcriptional functions of TFII-I by controlling its nuclear residency. MusTRD1/BEN has five or six direct repeats, each containing helix–loop–helix motifs, and, thus, belongs to the TFII-I family of transcription factors. TFII-I and MusTRD1/BEN, when expressed individually, show predominant nuclear localization. However, when the two proteins are coexpressed ectopically, MusTRD1/BEN locates almost exclusively to the nucleus, whereas TFII-I is largely excluded from the nucleus, resulting in a loss of TFII-I-dependent transcriptional activation of the c-fos promoter. Mutation of a consensus nuclear localization signal in MusTRD1/BEN results in a reversal of nuclear residency of the two proteins and a concomitant gain of c-fos promoter activity. These data suggest a means of transcriptional repression by competition at the level of nuclear occupancy.

Covalent assembly of a soluble T cell receptor-peptide-major histocompatibility class I complex.

We used stepwise photochemical cross-linking for specifically assembling soluble and covalent complexes made of a T-cell antigen receptor (TCR) and a class I molecule of the major histocompatibility complex (MHC) bound to an antigenic peptide. For that purpose, we have produced in myeloma cells a single-chain Fv construct of a TCR specific for a photoreactive H-2Kd-peptide complex. Photochemical cross-linking of this TCR single-chain Fv with a soluble form of the photoreactive H-2Kd-peptide ligand resulted in the formation of a ternary covalent complex. We have characterized the soluble ternary complex and showed that it reacted with antibodies specific for epitopes located either on the native TCR or on the Kd molecules. By preventing the fast dissociation kinetics observed with most T cell receptors, this approach provides a means of preparing soluble TCR-peptide-MHC complexes on large-scale levels.

Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes.

We have synthesized a recombinant gene encoding a single-chain HLA-A2/beta 2-microglobulin (beta 2m) molecule by linking beta 2m through its carboxyl terminus via a short peptide spacer to HLA-A2 (A*0201). This gene has been expressed in the beta 2m-deficient colorectal tumor cell line DLD-1. Transfection of this cell with the single-chain construct was associated with conformationally correct cell surface expression of a class I molecule of appropriate molecular mass. The single-chain HLA class I molecule presented either exogenously added peptide or (after interferon-gamma treatment) endogenously processed antigen to an influenza A matrix-specific, HLA-A2-restricted cytotoxic T-lymphocyte line. The need for interferon gamma for the processing and presentation of endogenous antigen suggests that DLD-1 has an antigen-processing defect that can be up-regulated, a feature that may be found in other carcinomas. Our data indicate that single-chain HLA class I constructs can form functional class I molecules capable of presenting endogenously processed antigens. Such molecules should be of use for functional studies, as well as providing potential anticancer immunotherapeutic agents or vaccines.

SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I.

Camptothecin is a potent antineoplastic agent that interferes with the action of eukaryotic DNA topoisomerase I; the covalent enzyme-DNA intermediate is reversibly stabilized, leading to G2 arrest and cell death. We used a genetic screen to identify cellular factors, other than DNA topoisomerase I, that participate in the process of camptothecin-induced cell death. Following ethyl methanesulfonate mutagenesis of top1 delta yeast cells expressing plasmid-borne wild-type DNA topoisomerase I, six dominant suppressors of camptothecin toxicity were isolated that define a single genetic locus, sct1. Mutant SCT1 cells expressed DNA topoisomerase I protein of similar specific activity and camptothecin sensitivity to that of congenic, drug-sensitive sct1 cells, yet were resistant to camptothecin-mediated lethality. Moreover, camptothecin-treated SCT1 cells did not exhibit the G2-arrested, terminal phenotype characteristic of drug-treated wild-type cells. SCT1 cell sensitivity to other DNA-damaging agents suggests that alterations in SCT1 function suppress camptothecin-induced DNA damage produced in the presence of yeast DNA topoisomerase I.

Scrambling of the actin I gene in two Oxytricha species.

The DNA in a germ-line nucleus (a micronucleus) undergoes extensive processing when it develops into a somatic nucleus (a macronucleus) after cell mating in hypotrichous ciliates. Processing includes destruction of a large amount of spacer DNA between genes and excision of gene-sized molecules from chromosomes. Before processing, micronuclear genes are interrupted by numerous noncoding segments called internal eliminated sequences (IESs). The IESs are excised and destroyed, and the retained macro-nuclear-destined sequences (MDSs) are spliced. MDSs in some micronuclear genes are not in proper order and must be reordered during processing to create functional gene-sized molecules for the macronucleus. Here we report that the micronuclear actin I gene in Oxytricha trifallax WR consists of 10 MDSs and 9 IESs compared to the previously reported 9 MDSs and 8 IESs in the micronuclear actin I gene of Oxytricha nova. The MDSs in the actin I gene are scrambled in a similar pattern in the two species, but the positions of MDS-IES junctions are shifted by up to 14 bp for scrambled and 138 bp for the nonscrambled MDSs. The shifts in MDS-IES junctions create differences in the repeat sequences that are believed to guide MDS splicing. Also, the sizes and sequences of IESs in the micronuclear actin I genes are different in the two Oxytricha species. These observations give insight about the possible origins of IES insertion and MDS scrambling in evolution and show the extraordinary malleability of the germ-line DNA in hypotrichs.

Complaint of Harvard President and Tutors against Nathan Prince, submitted to Governor William Shirley and the Board of Overseers on Jan. 29, 1741

President Edward Holyoke and Tutors Henry Flynt, Joseph Mayhew, and Thomas Marsh accused Prince of "sundry crimes & misdemeanors" and "sundry evil actions," including weakening and undermining the College government, showing contempt towards his fellow Tutors and towards Hollis Professor John Winthrop (who he claimed "knew no more of Philosophy than a Brute"), and making insulting remarks on numerous occasions. Prince was accused of calling others "Fool, Rogue, Rascal, Puppy &c." and of calling Col. Brattle "a Devilish Lyar." He was also accused of "appearing often times, to be what is commonly stil'd the worse for Drink" and of neglecting his duties towards his students.

List of further "instances of crimes and misdemeanors" allegedly committed by Nathan Prince (3 copies), Nov. 26, 1741

These three copies are not identical. One copy, which appears to be the original, is signed by Edward Holyoke, Henry Flynt, Joseph Mayhew, and Thomas Marsh. A note on the verso of one copy indicates that it was intended for delivery to Prince. Among many other things, the President and Tutors accused Prince of having said "in a Town meeting at Cambridge [...] that [Edmund Trowbridge] had not the manners to give him a pair of gloves at his Uncle's funeral."

The syntheses and characterization of nickel complexes; investigation of Ni(dppp)2 and [NiX(dppp)n]x, potentially catalytically active nickel(0)/(I) species for cross-coupling reactions

This thesis describes an investigation in which we compare Ni(0), Ni(I) and Ni(II) complexes containing 1,3-bis(diphenylphosphino)propane (dppp) as a phosphine ligand for their abilities to effect three types of cross-coupling reactions: Buchwald-Hartwig Amination, Heck-Mizoroki, and Suzuki-Miyaura cross-coupling reactions with different types of substrates. The Ni(0) complex Ni(dppp)2 is known and we have synthesized it via a new procedure involving zinc reduction of the known NiCl2(dppp) in the presence of an excess of dppp. The Ni(0) complex was characterized by NMR spectroscopy and X-ray crystallography. Since Ni(I) complexes of dppp seem unknown, we have synthesized what at this stage appear to be NiXdpppn/[NiX(dppp)n]x (X = Cl, Br, I; n = 1,2, x = 1, 2) by comproportionation of molar equivalents of Ni(dppp)2 and NiX2dppp, X= Cl, Br, I.

Kosowo - przed ostatecznym rozwiazaniem. Proces uregulowania statusu miedzynarodowego = uwarunkowania polityczne i historyczne perspektywy rozwoju sytuacji. Prace OSW 2008. Kosovo before the final decision. Regulation Kosovo's international status - historical and political conditions and prospects for future developments. OSW Study 27/2008

The question of Kosovo's status is currently one of the most important issues in international politics. Since 1999, Kosovo has been an international protectorate which was created in the aftermath of the NATO intervention to stop the brutal pacification of the Albanian insurgency by Serb forces. The province has since de facto become independent of Serbia. Resolution 1244 of the UN Security Council, which established the protectorate, does not preclude any possible outcome as regards its status. Aware that after the crimes of 1999, any attempt to re-integrate Kosovo into Serbia would lead to a massive Albanian uprising, the West has decided that the best solution would be to award Kosovo internationally supervised independence, while at the same time granting very wide autonomy to the Kosovo Serbs. Serbia and Russia rejected the solution proposed by the West, and so Kosovo became an arena of international rivalry for influence in the Western Balkans as well as another element of rivalry, transcending the regional dimension, between Russia and the West. Russia has been using the Kosovo case to build a new model of its relations with the United States and the EU. Since there is a group of countries sceptical about, or even opposed to, Kosovo's independence within the EU, the Kosovo settlement will be a test of the EU's ability to speak with one voice with regard to its external policy.

Vučić’s plebiscite almost slipped on arithmetics. EPC Commentary, 29 April 2016

As largely anticipated, the incumbent Prime Minister of Serbia, Aleksandar Vučić, secured another four years in power at the snap elections that took place on 24 April. However, the results suggest that Vučić has overplayed his hand with this personal plebiscite: simple arithmetics unmasked his exaggerated hope to wipe out the opposition and consolidate political dominance. This might bode well for political pluralism but voters’ preferences and the affixed party options caution against taking Serbia’s commitment to European integration for granted.

Boulder at northwestern corner of campus placed by Class of 1862

On verso of second copy of same print: Memorial of the Class of 1862. Placed on n.w. corner of campus in 1860. Removed in summer of 1969.

The picture gallery of Charles I.

Mode of access: Internet.

The works of Sir William Temple, bart. : to which is prefixed, the life and character of the author, considerably enlarged.

--I. Life of the author. An essay on the original and nature of government. Observations upon the united provinces of the Netherlands. Letters containing an account of the most important transactions that passed in Christendom from 1665 to 1672.-II. Sequel of the author's letters, serving to supply the loss of the first part of his memoirs. A survey of the constitutions and interests of the empire, Sweden, Denmark, Spain, Holland, France, and Flanders in 1671. A letter to the Duke of Ormond, written in October 1673. Memoirs, pt. II--III.--III. [Essays] Poetry.--IV. Letters to the king, the Prince of Orange, &c. Index.

Memalik-i Osmaniyede Kral Rakoçi ve tevabii, 1109-1154 /

"Macar kahramanı Rakoçi Ferenç ve oğlu Rakoçi Yojef ve tevabiinin memalik-i Osmaniyeye iltica ettikleri sırada cereyan eden hadisata dair bir medhali ve Divan-ı Hümayunun gayri matbuu vesaiklerini muhtevidir"--T.p.

Heinrich Heine und Napoleon I. /

Includes bibliographical references and index.