Multiple conformational states in crystals and in solution in alpha gamma hybrid peptides. Fragility of the C-12 helix in short sequences

The conformational properties of foldamers generated from alpha gamma hybrid peptide sequences have been probed in the model sequence Boc-Aib-Gpn-Aib-Gpn-NHMe. The choice of alpha-aminoisobutyryl (Aib) and gabapentin (Gpn) residues greatly restricts sterically accessible coil formational space. This model sequence was anticipated to be a short segment of the alpha gamma C-12 helix, stabilized by three successive 4 -> 1 hydrogen bonds, corresponding to a backbone-expanded analogue of the alpha polypeptide 3(10)-helix. Unexpectedly, three distinct crystalline polymorphs were characterized in the solid state by X-ray diffraction. In one form, two successive C-12 hydrogen bonds were obtained at the N-terminus, while a novel C-17 hydrogen-bonded gamma alpha gamma turn was observed at the C-terminus. In the other two polymorphs, isolated C-9 and C-7 hydrogen-bonded turns were observed at Gpn (2) and Gpn (4). Isolated C-12 and C-9 turns were also crystallographically established in the peptides Boc-Aib-Gpn-Aib-OMe and Boc-Gpn-Aib-NHMe, respectively. Selective line broadening of NH resonances and the observation of medium range NH(i)<-> NH(i+2) NOEs established the presence of conformational heterogeneity for the tetrapeptide in CDCl3 solution. The NMR results are consistent with the limited population of the continuous C-12 helix conformation. Lengthening of the (alpha gamma)(n) sequences in the nonapeptides Boc-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Xxx (Xxx = Aib, Leu) resulted in the observation of all of the sequential NOEs characteristic of an alpha gamma C-12 helix. These results establish that conformational fragility is manifested in short hybrid alpha gamma sequences despite the choice of conformationally constrained residues, while stable helices are formed on chain extension.

Towards a United States of Africa? Combining Zambian and AU level debate.

Globalisaatio on luonut uuden maailmanjärjestelmän jonka myötä yksittäisten valtioiden vaikutusvalta on vähentynyt entisestään. Tämä pitää paikkansa erityisesti kehittyvien maiden kohdalla, esimerkiksi Afrikassa. Afrikka on pyrkinyt taistelemaan globalisaation tuomia negatiivisia vaikutuksia vastaan alueellistumisen ja maanosan yhtenäisyyttä ajavien hankkeiden kautta jo vuosikymmenien ajan, mutta toistaiseksi tulokset eivät ole olleet vakuttavia. Tällä hetkellä Afrikan Unionissa keskustellaan hankkeesta muodostaa Afrikan Yhdysvallat. Aiemmista hankkeista poiketen tämän uuden aloitteen ajatus perustuu ylikansallisuudelle, jossa yksittäiset valtiot luovuttavat valtaansa ylikansallisille elimille, kuten Afrikan Unionin hallitukselle. Näin ollen on tärkeää tarkastella aloitetta Afrikan Yhdysvaltojen perustamiseksi ja arvioida, voisiko tällainen ylikansallinen organisaatio auttaa Afrikkaa kääntämään globalisaation haittavaikutukset myönteisiksi. Tämä Pro Gradu-tutkielma väittää sen olevan mahdollista, mutta vain siinä tapauksessa että Afrikka on valmis hyväksymään yhtenäisyyden rajoitukset. Aiemman tutkimuksen vähyyden vuoksi on myös tarpeen tutkia Afrikan Yhdysvalloista kansallisilla tasoilla käytävää keskustelua. Tämän vuoksi tässä tutkielmassa painotetaan esimerkkimaa Sambian kautta yhden Afrikan Unionin jäsenmaan keskinäistä keskustelua aiheesta ja verrataan sitä Afrikan Unionin tason keskusteluun. Tutkielma sisältää kirjallisuuskatsauksen sekä tapaustutkimuksen. Tutkimusaineisto koostuu sambialaisista sanomalehtiotteista sekä Sambian valtion ja Afrikan Unionin virallisista asiakirjoista. Pääasiallisena tutkimusmenetelmänä on laadullinen sisällönanalyysi. Teoreettinen viitekehys perustuu afrikkalaisen valtion ja kansalaisyhteiskunnan, alueellistumisen, globalisaation hallinnan, pan-afrikkalaisuuden ja poliittisen integraation teorioihin sekä historialliseen katsaukseen Afrikan yhtenäisyydestä. Perimmäisenä tarkoituksena on lisätä ymmärrystä afrikkalaisesta valtiosta ja politiikasta. Tutkimuksen tulosten mukaan on havaittavissa aukko valtioiden virallisten toimijoiden näkemysten ja kansalaisyhteiskunnan huolenaiheiden välillä. Viralliset toimijat näyttävät olevan kansalaisyhteiskuntaa vahvemmin Afrikan Yhdysvaltojen kannalla. Virallisten toimijoiden korostaessa Afrikan aatteellista yhtenäisyyttä kansalaisyhteiskunta on huolissaan sen toteutumisesta käytännössä. Esiin nousee myös kysymys 'afrikkalaisesta' identiteetistä ja kansalaisuudesta sekä kommunikaatiosta valtion ja kansalaisten välillä.

Measurement of the b-hadron production cross section using decays to μ-D0X final states in pp̅ collisions at √s=1.96 TeV

We report a measurement of the production cross section for b hadrons in pp̅ collisions at √s=1.96  TeV. Using a data sample derived from an integrated luminosity of 83  pb-1 collected with the upgraded Collider Detector (CDF II) at the Fermilab Tevatron, we analyze b hadrons, Hb, partially reconstructed in the semileptonic decay mode Hb→μ-D0X. Our measurement of the inclusive production cross section for b hadrons with transverse momentum pT>9  GeV/c and rapidity |y|<0.6 is σ=1.30  μb±0.05  μb(stat)±0.14  μb(syst)±0.07  μb(B), where the uncertainties are statistical, systematic, and from branching fractions, respectively. The differential cross sections dσ/dpT are found to be in good agreement with recent measurements of the Hb cross section and well described by fixed-order next-to-leading logarithm predictions.

Measurement of the b-hadron production cross section using decays to μ-D0X final states in pp̅ collisions at √s=1.96 TeV

We report a measurement of the production cross section for b hadrons in pp̅ collisions at √s=1.96  TeV. Using a data sample derived from an integrated luminosity of 83  pb-1 collected with the upgraded Collider Detector (CDF II) at the Fermilab Tevatron, we analyze b hadrons, Hb, partially reconstructed in the semileptonic decay mode Hb→μ-D0X. Our measurement of the inclusive production cross section for b hadrons with transverse momentum pT>9  GeV/c and rapidity |y|<0.6 is σ=1.30  μb±0.05  μb(stat)±0.14  μb(syst)±0.07  μb(B), where the uncertainties are statistical, systematic, and from branching fractions, respectively. The differential cross sections dσ/dpT are found to be in good agreement with recent measurements of the Hb cross section and well described by fixed-order next-to-leading logarithm predictions.

Svetlichny's inequality and genuine tripartite nonlocality in three-qubit pure states

The violation of the Svetlichny's inequality (SI) [Phys. Rev. D 35, 3066 (1987)] is sufficient but not necessary for genuine tripartite nonlocal correlations. Here we quantify the relationship between tripartite entanglement and the maximum expectation value of the Svetlichny operator (which is bounded from above by the inequality) for the two inequivalent subclasses of pure three-qubit states: the Greenberger-Horne-Zeilinger (GHZ) class and the W class. We show that the maximum for the GHZ-class states reduces to Mermin's inequality [Phys. Rev. Lett. 65, 1838 (1990)] modulo a constant factor, and although it is a function of the three tangle and the residual concurrence, large numbers of states do not violate the inequality. We further show that by design SI is more suitable as a measure of genuine tripartite nonlocality between the three qubits in the W-class states,and the maximum is a certain function of the bipartite entanglement (the concurrence) of the three reduced states, and only when their sum attains a certain threshold value do they violate the inequality.

Measurement of the b-hadron production cross section using decays to μ-D0X final states in pp̅ collisions at √s=1.96 TeV

We report a measurement of the production cross section for b hadrons in p-pbar collisions at sqrt{s}=1.96 TeV. Using a data sample derived from an integrated luminosity of 83 pb^-1 collected with the upgraded Collider Detector (CDF II) at the Fermilab Tevatron, we analyze b hadrons, H_b, partially reconstructed in the semileptonic decay mode H_b -> mu^- D^0 X. Our measurement of the inclusive production cross section for b hadrons with transverse momentum p_T > 9 GeV/c and rapidity |y|

Non-destructive discrimination of Bell states by NMR using a single ancilla qubit

Discrimination of Bell states plays an important role in a number of quantum computational protocols such as teleportation and secret sharing. However, most of the protocols dealing with Bell state discrimination in the literature either involve performing correlated measurements or destroying the entanglement of the system. Here, we demonstrate an NMR-based experimental realization of a protocol for Bell state discrimination, following a scheme proposed by Gupta et al (quant-ph/0504183v1, 23 April 2005), which does not destroy the Bell state under consideration. Using the proposed protocol, one can deterministically distinguish the Bell states, without performing a measurement using the entangled basis. State discrimination is performed through two independent measurements on one ancilla qubit, which leaves the Bell states unchanged.

Excited-state structures of molecules with nearby electronic states

Vibronic coupling among the nearby excited electronic states via the in-plane and the out-of-plane nuclear motions is examined in benzene, pyrazine, formaldehyde and thioformaldehyde. Results reveal that in benzene the structure distorts via the most active nuclear bending (planar) motion while in the other molecules the structures distort through an out-of-plane bending motion in their respective lowest excited states.

Photochemistry of .alpha.,.beta.-unsaturated thiones. Cycloaddition to electron-deficient olefins from higher excited states

Electron-deficient olefins add to thioenone 1 upon m* excitation. Cycloaddition occurs to the thiocarbonyl chromophore preferentially from the less-hindered side to yield thietanes. Thietane formation is stereospecific and regioselective. This addition has been inferred to originate from the second excited singlet, S2(?rx*), state. The exciplex intermediacy has been inferred from the dependence of the fluorescence quenching rate constant on the electron-acceptor properties of the olefin. The observed site specificity and regioselectivity are rationalized on the basis of PMO theory. The observed photochemical behavior of thioenone is different from that of enones.

Crystal Structure of Staphylococcus aureus Metallopeptidase (Sapep) Reveals Large Domain Motions between the Manganese-bound and Apo-states

Proteases belonging to the M20 family are characterized by diverse substrate specificity and participate in several metabolic pathways. The Staphylococcus aureus metallopeptidase, Sapep, is a member of the aminoacylase-I/M20 protein family. This protein is a Mn2+-dependent dipeptidase. The crystal structure of this protein in the Mn2+-bound form and in the open, metal-free state suggests that large interdomain movements could potentially regulate the activity of this enzyme. We note that the extended inactive conformation is stabilized by a disulfide bond in the vicinity of the active site. Although these cysteines, Cys(155) and Cys(178), are not active site residues, the reduced form of this enzyme is substantially more active as a dipeptidase. These findings acquire further relevance given a recent observation that this enzyme is only active in methicillin-resistant S. aureus. The structural and biochemical features of this enzyme provide a template for the design of novel methicillin-resistant S. aureus-specific therapeutics.

Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients

Background: Molecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth. A recent study has demonstrated that clinical isolates of the parasite have distinct physiological states, one of which resembles environmental stress response showing up-regulation of specific molecular chaperones. Methods: Chaperone networks operational in the distinct physiological clusters in clinical malaria parasites were constructed using cytoscape by utilizing their clinical expression profiles. Results: Molecular chaperones show distinct profiles in the previously defined physiologically distinct states. Further, expression profiles of the chaperones from different cellular compartments correlate with specific patient clusters. While cluster 1 parasites, representing a starvation response, show up-regulation of organellar chaperones, cluster 2 parasites, which resemble active growth based on glycolysis, show up-regulation of cytoplasmic chaperones. Interestingly, cytoplasmic Hsp90 and its co-chaperones, previously implicated as drug targets in malaria, cluster in the same group. Detailed analysis of chaperone expression in the patient cluster 2 reveals up-regulation of the entire Hsp90-dependent pro-survival circuitries. In addition, cluster 2 also shows up-regulation of Plasmodium export element (PEXEL)-containing Hsp40s thought to have regulatory and host remodeling roles in the infected erythrocyte. Conclusion: In all, this study demonstrates an intimate involvement of parasite-encoded chaperones, PfHsp90 in particular, in defining pathogenesis of malaria.