Kirjallisuusosa: Alzheimerin taudin rottamallien vastaavuus tautiin ihmisessä ja mallien käyttökelpoisuus

Kirjallisuusosa: Alzheimerin taudin hoitoon olisi tarvetta uusille taudinkulkuun vaikuttaville lääkeaineille. Niiden kehittämiseksi tarvitaan eläinmalleja, joissa esiintyy taudin patofysiologisia piirteitä. Rottamalleista vanhemmat skopolamiini- tai MK-801-häirintä sekä ikääntyneiden rottien käyttö eivät kovin hyvin vastaa taudin patofysiologiaa, vaikka niissä eläimen muisti käyttäytymiskokeissa onkin heikentynyt. Uudemmat transgeeniset rottamallit ja mallit, joissa annetaan Aβ:a aivoihin, ilmentävät huomattavasti paremmin Alzheimerin taudin kaltaista tilaa aivoissa ainakin Aβ:n osalta. Taupatofysiologiaa ei silti kummassakaan näistä malleista juuri esiinny. Toisaalta Aβ:lla näyttäisi olevan huomattavasti tau:ta suurempi rooli taudissa, joten sen ilmeneminen mallissa onkin keskeisempi tekijä. Nämä mallit ilmentävät melko suurelti osin yhtä hyvin Alzheimerin taudin patofysiologiaa. Aβ:n antaminen on hieman yksinkertaisempi suorittaa käytännössä, sillä siinä ei tarvitse luoda transgeenista kantaa. Toisaalta transgeenisessa mallissa Aβ-patofysiologia syntyy enemmän Alzheimerin taudin kaltaisesti solujen sisällä eikä valmiita aggregoituvia Aβ-peptidejä anneta ulkopuolelta aivoihin. Molemmat mallit ovat kuitenkin käyttökelpoisia, ja soveltuvat erityisesti Aβ:an vaikuttavien lääkeaineiden kehittämiseen. Kokeellinen osa: Kokeen tarkoituksena oli validoida kohotettu ristikko-sokkelo (elevated plus-maze, EPM) hiirillä kognitiomallina. Kokeessa käytettiin kahden koekerran (trial, T) menetelmää, jossa koekertojen pituus oli viisi minuuttia. Näin saatiin useita oppimista kuvaavia parametreja. Hiirille yritettiin saada muistihäiriö aikaviiveen avulla (koekertojen väli 1-18 vrk) tai antamalla muskariinireseptoriantagonistia skopolamiinia (0,1-0,8 mg/kg i.p.) 30 minuuttia ennen T1:tä. Nämä kokeet suoritettiin sekä C57BL/6J- että ICR:(CD-1)-hiirillä. Aikaviivekokeissa ainut ryhmä, jolla oli viitettä unohtamisesta, oli ICR:(CD-1)-hiirien 18 vrk:n ryhmä. Tämän perusteella tutkittiin vielä 21 vuorokauden aikaväli, mutta selvää muistihäiriötä ei esiintynyt. Skopolamiini ei häirinnyt muistia ICR:(CD-1)-hiirillä, mutta C57BL/6J-hiirillä 0,2 mg/kg:n annoksesta ylöspäin merkitsevä muistihäiriö esiintyi. Näin ollen jatkokokeissa käytettäväksi valittiin skopolamiinin annos 0,2 mg/kg C57BL/6J-hiirillä, ja siinä tutkittiin donepetsiilin (0,3, 0,8 ja 1,5 mg/kg s.c), memantiinin (5,0 ja 10,0 mg/kg s.c) ja kokeellisen 5-HT6-antagonistin SB742457:n (1,5 ja 6,0 mg/kg s.c) muistia parantavia vaikutuksia. Tutkittavat lääkeaineet annettiin 40 minuuttia ennen T1:tä ja skopolamiini 30 minuuttia ennen. Memantiinilla (5,0 mg/kg) oli selkeä skopolamiinin heikentämää kognitiota parantava vaikutus ja donepetsiilillakin (1,5 mg/kg) suuntaus tähän. Tulosten perusteella malli näyttäisi soveltuvan muisti- ja oppimisvaikutusten tutkimiseen käytettäväksi malliksi.

Search for single top quark production in pp̅ collisions at √s=1.96 TeV in the missing transverse energy plus jets topology

We report a search for single top quark production with the CDF II detector using 2.1 fb-1 of integrated luminosity of pbar p collisions at sqrt{s}=1.96 TeV. The data selected consist of events characterized by large energy imbalance in the transverse plane and hadronic jets, and no identified electrons and muons, so the sample is enriched in W -> tau nu decays. In order to suppress backgrounds, additional kinematic and topological requirements are imposed through a neural network, and at least one of the jets must be identified as a b-quark jet. We measure an excess of signal-like events in agreement with the standard model prediction, but inconsistent with a model without single top quark production by 2.1 standard deviations (sigma), with a median expected sensitivity of 1.4 sigma. Assuming a top quark mass of 175 GeV/c2 and ascribing the excess to single top quark production, the cross section is measured to be 4.9+2.5-2.2(stat+syst)pb, consistent with measurements performed in independent datasets and with the standard model prediction.

Top quark mass measurement in the lepton plus jets channel using a modified matrix element method

We report a measurement of the top quark mass, m_t, obtained from ppbar collisions at sqrt(s) = 1.96 TeV at the Fermilab Tevatron using the CDF II detector. We analyze a sample corresponding to an integrated luminosity of 1.9 fb^-1. We select events with an electron or muon, large missing transverse energy, and exactly four high-energy jets in the central region of the detector, at least one of which is tagged as coming from a b quark. We calculate a signal likelihood using a matrix element integration method, with effective propagators to take into account assumptions on event kinematics. Our event likelihood is a function of m_t and a parameter JES that determines /in situ/ the calibration of the jet energies. We use a neural network discriminant to distinguish signal from background events. We also apply a cut on the peak value of each event likelihood curve to reduce the contribution of background and badly reconstructed events. Using the 318 events that pass all selection criteria, we find m_t = 172.7 +/- 1.8 (stat. + JES) +/- 1.2 (syst.) GeV/c^2.

Search for WW and WZ production in lepton plus jets final state at CDF

We present a search for WW and WZ production in final states that contain a charged lepton (electron or muon) and at least two jets, produced in sqrt(s) = 1.96 TeV ppbar collisions at the Fermilab Tevatron, using data corresponding to 1.2 fb-1 of integrated luminosity collected with the CDF II detector. Diboson production in this decay channel has yet to be observed at hadron colliders due to the large single W plus jets background. An artificial neural network has been developed to increase signal sensitivity, as compared with an event selection based on conventional cuts. We set a 95% confidence level upper limit of sigma_{WW}* BR(W->lnu,W->jets)+ sigma_{WZ}*BR(W->lnu,Z->jets)

Measurement of the tt̅ cross section in pp̅ collisions at √s=1.96 TeV using dilepton events with a lepton plus track selection

This paper reports a measurement of the cross section for the pair production of top quarks in ppbar collisions at sqrt(s) = 1.96 TeV at the Fermilab Tevatron. The data was collected from the CDF II detector in a set of runs with a total integrated luminosity of 1.1 fb^{-1}. The cross section is measured in the dilepton channel, the subset of ttbar events in which both top quarks decay through t -> Wb -> l nu b where l = e, mu, or tau. The lepton pair is reconstructed as one identified electron or muon and one isolated track. The use of an isolated track to identify the second lepton increases the ttbar acceptance, particularly for the case in which one W decays as W -> tau nu. The purity of the sample may be further improved at the cost of a reduction in the number of signal events, by requiring an identified b-jet. We present the results of measurements performed with and without the request of an identified b-jet. The former is the first published CDF result for which a b-jet requirement is added to the dilepton selection. In the CDF data there are 129 pretag lepton + track candidate events, of which 69 are tagged. With the tagging information, the sample is divided into tagged and untagged sub-samples, and a combined cross section is calculated by maximizing a likelihood. The result is sigma_{ttbar} = 9.6 +/- 1.2 (stat.) -0.5 +0.6 (sys.) +/- 0.6 (lum.) pb, assuming a branching ratio of BR(W -> ell nu) = 10.8% and a top mass of m_t = 175 GeV/c^2.

Measurement of the top quark mass at CDF using the “neutrino ϕ weighting” template method on a lepton plus isolated track sample

We present a measurement of the top quark mass with t-tbar dilepton events produced in p-pbar collisions at the Fermilab Tevatron $\sqrt{s}$=1.96 TeV and collected by the CDF II detector. A sample of 328 events with a charged electron or muon and an isolated track, corresponding to an integrated luminosity of 2.9 fb$^{-1}$, are selected as t-tbar candidates. To account for the unconstrained event kinematics, we scan over the phase space of the azimuthal angles ($\phi_{\nu_1},\phi_{\nu_2}$) of neutrinos and reconstruct the top quark mass for each $\phi_{\nu_1},\phi_{\nu_2}$ pair by minimizing a $\chi^2$ function in the t-tbar dilepton hypothesis. We assign $\chi^2$-dependent weights to the solutions in order to build a preferred mass for each event. Preferred mass distributions (templates) are built from simulated t-tbar and background events, and parameterized in order to provide continuous probability density functions. A likelihood fit to the mass distribution in data as a weighted sum of signal and background probability density functions gives a top quark mass of $165.5^{+{3.4}}_{-{3.3}}$(stat.)$\pm 3.1$(syst.) GeV/$c^2$.

Search for New Physics with a Dijet Plus Missing ET Signature in pp̅ Collisions at √s=1.96 TeV

We present results of a signature-based search for new physics using a dijet plus missing transverse energy data sample collected in 2 fb-1 of p-pbar collisions at sqrt(s) = 1.96 TeV with the CDF II detector at the Fermilab Tevatron. We observe no significant event excess with respect to the standard model prediction and extract a 95% C.L. upper limit on the cross section times acceptance for a potential contribution from a non-standard model process. Based on this limit the mass of a first or second generation scalar leptoquark is constrained to be above 187 GeV/c^2.

Measurement of the tt̅ production cross section in 2 fb-1 of pp̅ collisions at √s=1.96 TeV using lepton plus jets events with soft muon b tagging

We present a measurement of the tt̅ production cross section in pp̅ collisions at √s=1.96  TeV using events containing a high transverse momentum electron or muon, three or more jets, and missing transverse energy. Events consistent with tt̅ decay are found by identifying jets containing candidate heavy-flavor semileptonic decays to muons. The measurement uses a CDF run II data sample corresponding to 2  fb-1 of integrated luminosity. Based on 248 candidate events with three or more jets and an expected background of 79.5±5.3 events, we measure a production cross section of 9.1±1.6  pb.

Measurement of the tt̅ production cross section in 2 fb-1 of pp̅ collisions at √s=1.96 TeV using lepton plus jets events with soft muon b tagging

We present a measurement of the tt̅ production cross section in pp̅ collisions at √s=1.96  TeV using events containing a high transverse momentum electron or muon, three or more jets, and missing transverse energy. Events consistent with tt̅ decay are found by identifying jets containing candidate heavy-flavor semileptonic decays to muons. The measurement uses a CDF run II data sample corresponding to 2  fb-1 of integrated luminosity. Based on 248 candidate events with three or more jets and an expected background of 79.5±5.3 events, we measure a production cross section of 9.1±1.6  pb.

Measurement of the tt̅ production cross section in 2 fb-1 of pp̅ collisions at √s=1.96 TeV using lepton plus jets events with soft muon b tagging

We present a measurement of the $\ttbar$ production cross section in $\ppbar$ collisions at $\sqrt{s}=1.96$ TeV using events containing a high transverse momentum electron or muon, three or more jets, and missing transverse energy. Events consistent with $\ttbar$ decay are found by identifying jets containing candidate heavy-flavor semileptonic decays to muons. The measurement uses a CDF Run II data sample corresponding to $2 \mathrm{fb^{-1}}$ of integrated luminosity. Based on 248 candidate events with three or more jets and an expected background of $79.5\pm5.3$ events, we measure a production cross section of $9.1\pm 1.6 \mathrm{pb}$.