Low major histocompatibility complex class II diversity in European and North American moose.

Major histocompatibility complex (MHC) genes encode cell surface proteins whose function is to bind and present intracellularly processed peptides to T lymphocytes of the immune system. Extensive MHC diversity has been documented in many species and is maintained by some form of balancing selection. We report here that both European and North American populations of moose (Alces alces) exhibit very low levels of genetic diversity at an expressed MHC class II DRB locus. The observed polymorphism was restricted to six amino acid substitutions, all in the peptide binding site, and four of these were shared between continents. The data imply that the moose have lost MHC diversity in a population bottleneck, prior to the divergence of the Old and New World subspecies. Sequence analysis of mtDNA showed that the two subspecies diverged at least 100,000 years ago. Thus, viable moose populations with very restricted MHC diversity have been maintained for a long period of time. Both positive selection for polymorphism and intraexonic recombination have contributed to the generation of MHC diversity after the putative bottleneck.

Crystal structure of an H-2Kb-ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove.

Sequence analysis of peptides naturally presented by major histocompatibility complex (MHC) class I molecules has revealed allele-specific motifs in which the peptide length and the residues observed at certain positions are restricted. Nevertheless, peptides containing the standard motif often fail to bind with high affinity or form physiologically stable complexes. Here we present the crystal structure of a well-characterized antigenic peptide from ovalbumin [OVA-8, ovalbumin-(257-264), SIINFEKL] in complex with the murine MHC class I H-2Kb molecule at 2.5-A resolution. Hydrophobic peptide residues Ile-P2 and Phe-P5 are packed closely together into binding pockets B and C, suggesting that the interplay of peptide anchor (P5) and secondary anchor (P2) residues can couple the preferred sequences at these positions. Comparison with the crystal structures of H-2Kb in complex with peptides VSV-8 (RGYVYQGL) and SEV-9 (FAPGNYPAL), where a Tyr residue is used as the C pocket anchor, reveals that the conserved water molecule that binds into the B pocket and mediates hydrogen bonding from the buried anchor hydroxyl group could not be likewise positioned if the P2 side chain were of significant size. Based on this structural evidence, H-2Kb has at least two submotifs: one with Tyr at P5 (or P6 for nonamer peptides) and a small residue at P2 (i.e., Ala or Gly) and another with Phe at P5 and a medium-sized hydrophobic residue at P2 (i.e., Ile). Deciphering of these secondary submotifs from both crystallographic and immunological studies of MHC peptide binding should increase the accuracy of T-cell epitope prediction.

QSAR e dinâmica molecular no estudo de sistemas biomoleculares: predição da atividade biológica de antagonistas do receptor sigma-1 e simulações de bicamadas lipídicas

Diferentes abordagens teóricas têm sido utilizadas em estudos de sistemas biomoleculares com o objetivo de contribuir com o tratamento de diversas doenças. Para a dor neuropática, por exemplo, o estudo de compostos que interagem com o receptor sigma-1 (Sig-1R) pode elucidar os principais fatores associados à atividade biológica dos mesmos. Nesse propósito, estudos de Relações Quantitativas Estrutura-Atividade (QSAR) utilizando os métodos de regressão por Mínimos Quadrados Parciais (PLS) e Rede Neural Artificial (ANN) foram aplicados a 64 antagonistas do Sig-1R pertencentes à classe de 1-arilpirazóis. Modelos PLS e ANN foram utilizados com o objetivo de descrever comportamentos lineares e não lineares, respectivamente, entre um conjunto de descritores e a atividade biológica dos compostos selecionados. O modelo PLS foi obtido com 51 compostos no conjunto treinamento e 13 compostos no conjunto teste (r² = 0,768, q² = 0,684 e r²teste = 0,785). Testes de leave-N-out, randomização da atividade biológica e detecção de outliers confirmaram a robustez e estabilidade dos modelos e mostraram que os mesmos não foram obtidos por correlações ao acaso. Modelos também foram gerados a partir da Rede Neural Artificial Perceptron de Multicamadas (MLP-ANN), sendo que a arquitetura 6-12-1, treinada com as funções de transferência tansig-tansig, apresentou a melhor resposta para a predição da atividade biológica dos compostos (r²treinamento = 0,891, r²validação = 0,852 e r²teste = 0,793). Outra abordagem foi utilizada para simular o ambiente de membranas sinápticas utilizando bicamadas lipídicas compostas por POPC, DOPE, POPS e colesterol. Os estudos de dinâmica molecular desenvolvidos mostraram que altas concentrações de colesterol induzem redução da área por lipídeo e difusão lateral e aumento na espessura da membrana e nos valores de parâmetro de ordem causados pelo ordenamento das cadeias acil dos fosfolipídeos. As bicamadas lipídicas obtidas podem ser usadas para simular interações entre lipídeos e pequenas moléculas ou proteínas contribuindo para as pesquisas associadas a doenças como Alzheimer e Parkinson. As abordagens usadas nessa tese são essenciais para o desenvolvimento de novas pesquisas em Química Medicinal Computacional.

Desilication of TS-1 zeolite for the oxidation of bulky molecules

A series of modified TS-1 samples have been produced by desilication of the original TS-1 (4 wt.% Ti) using a chemical treatment with NaOH. Desilicated TS-1 zeolites exhibit a large BET surface area together with a well-developed mesoporosity. The hierarchical catalysts from desilication of TS-1 zeolite show a good catalytic activity for the oxidation of small molecules and a significantly higher activity for the oxidation of bulky molecules.

Exhortation read to 27 of the Sophomore class, 1797 July 1

9-page handwritten copy of an address by Eliphalet Pearson read to twenty-seven members of the sophomore class after an incident on June 27, 1797 in which "in direct violation of College law a majority of the sophomore class repaired to the house of Richard Boardman in this town; that they did then & there indulge to a free use of wine" that incited them to drunkenly parade through town and disturb the evening church services of the College.

White on corporations : containing the laws as amended to January 1, 1902, concerning business, railroad, ferry ... corporations, joint-stock associations, etc. ... also all state and federal statutes affecting the class of corporations above enumerated, together with decisions, annotations and forms /

Mode of access: Internet.

Intermediate (field) (direct and general support) and depot level maintenance manual : generator set, diesel engine driven, tactical skid mtd 5kw, 1 phase - 2 wire, 1 phase - 3 wire, 3 phase - 4 wire, 120, 120/240 and 120/208 volts, DoD model MEP-002A, class utility, hertz 60, NSN 6115-00-465-1044.

"July 1977."

Operator and organizational maintenance manual : generator set, diesel engine driven, tactical skid mtd 5kw, 1 phase - 2 wire, 1 phase - 3 wire, 3 phase - 4 wire, 120, 120/240 and 120/208 volts : DoD model MEP-002A, class utility, hertz 60, NSN 6115-00-465-1044.

"July 1977."

Organizational and direct support, repair parts, and special tools list for drill, pneumatic, drifter, crawler mounted, self propelled, dry type, 220 lb class, minimum 4-1/2 inch bore, power feed, 1-1/2 inch lugged shank chuck w/ 12 each [sic] shank rock drill (Chicago Pneumatic Tool Company model G-900) (NSN 3820-00-930-1917).

"May 1976."

Operator and organizational maintenance manual : generator set, diesel engine driven, tactical skid MTD 10KW, 1 phase-2 wire, 1 phase-3 wire, 3 phase-4 wire, 120, 120/240 and 120/208 volts, DoD model MEP-003A, class utility, Hertz 60, NSN 6115-00-465-1033.

Includes index.

Intermediate (field) (direct and general support) and depot level maintenance manual : generator set, diesel engine driven, tactical skid MTD 5KW, 1 phase-2 wire, 1 phase-3 wire, 3 phase-4 wire, 120, 120/240 and 120/208 volts, DoD model MEP-002A, class utility, hertz 60, NSN 6115-00-465-1044.

"July 1977."

Organizational, direct support, and general support maintenance repair parts and special tools list (including depot maintenance repair parts and special tools) : generator set, diesel engine driven, tactical skid MTD 10 kW, 1 phase-2 wire, 1 phase-3 wire, 3 phase-4 wire, 120, 120/240 and 120/208 volts : DoD model MEP-003A ... class utility ... hertz 60 ... 6115-00-465-1027.

"SL-4-05684C/06585B."

Intermediate (field) (direct and general support) and depot level maintenance manual : generator set, diesel engine driven, tactical skid MTD 10KW, 1 phase-2 wire, 1 phase-3 wire, 3 phase-4 wire, 120, 120/240 and 120/208 volts : DoD model MEP-003A, class utility, hertz 60, NSN 6115-00-465-1030.

"July 1977."

Operator and organizational maintenance manual : generator set, diesel engine driven, tactical skid mtd 5KW, 1 phase-2 wire, 1 phase-3 wire, 3 phase-4 wire, 120, 120/240 and 120/208 volts, DoD model MEP-002A, class utility, Hertz 60, NSN 6115-00-465-1044.

"July 1977."

Operator and organizational maintenance manual : generator set, diesel engine driven, tactical skid mtd 10kw, 1 phase - 2 wire, 1 phase - 3 wire, 3 phase - 4 wire, 120, 120/240, and 120/208 volts, DoD model MEP-003A, class utility, hertz 60, NSN 6115-00-465-1030.

"July 1977."