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We report results on rho (770)0--> pi + pi - production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[sNN]=200 GeV. This is the first direct measurement of rho (770)0--> pi + pi - in heavy-ion collisions. The measured rho 0 peak in the invariant mass distribution is shifted by ~40 MeV/c2 in minimum bias p+p interactions and ~70 MeV/c2 in peripheral Au+Au collisions. The rho 0 mass shift is dependent on transverse momentum and multiplicity. The modification of the rho 0 meson mass, width, and shape due to phase space and dynamical effects are discussed.
We report the first observations of the first harmonic (directed flow, v1) and the fourth harmonic (v4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v2) generated at RHIC. From the correlation of v2 with v1 it is determined that v2 is positive, or in-plane. The integrated v4 is about a factor of 10 smaller than v2. For the sixth (v6) and eighth (v8) harmonics upper limits on the magnitudes are reported.
We present STAR measurements of charged hadron production as a function of centrality in Au+Au collisions at sqrt[sNN ]=130 GeV . The measurements cover a phase space region of 0.2< pT <6.0 GeV/c in transverse momentum and -1< eta <1 in pseudorapidity. Inclusive transverse momentum distributions of charged hadrons in the pseudorapidity region 0.5< | eta | <1 are reported and compared to our previously published results for | eta | <0.5 . No significant difference is seen for inclusive pT distributions of charged hadrons in these two pseudorapidity bins. We measured dN/d eta distributions and truncated mean pT in a region of pT > pcutT , and studied the results in the framework of participant and binary scaling. No clear evidence is observed for participant scaling of charged hadron yield in the measured pT region. The relative importance of hard scattering processes is investigated through binary scaling fraction of particle production.
Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at sqrt[sNN]=200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in p+p at the same energy. The elliptic anisotropy v2 is found to reach its maximum at pt~3 GeV/c, then decrease slowly and remain significant up to pt ~ 7-10 GeV/c. Stronger suppression is found in the back-to-back high-pt particle correlations for particles emitted out of plane compared to those emitted in plane. The centrality dependence of v2 at intermediate pt is compared to simple models based on jet quenching.
Transverse energy ( ET ) distributions have been measured for Au+Au collisions at sqrt[sNN ]=200 GeV by the STAR Collaboration at RHIC. ET is constructed from its hadronic and electromagnetic components, which have been measured separately. ET production for the most central collisions is well described by several theoretical models whose common feature is large energy density achieved early in the fireball evolution. The magnitude and centrality dependence of ET per charged particle agrees well with measurements at lower collision energy, indicating that the growth in ET for larger collision energy results from the growth in particle production. The electromagnetic fraction of the total ET is consistent with a final state dominated by mesons and independent of centrality.
We present data on e+ e- pair production accompanied by nuclear breakup in ultraperipheral gold-gold collisions at a center of mass energy of 200 GeV per nucleon pair. The nuclear breakup requirement selects events at small impact parameters, where higher-order diagrams for pair production should be enhanced. We compare the data with two calculations: one based on the equivalent photon approximation, and the other using lowest-order quantum electrodynamics (QED). The data distributions agree with both calculations, except that the pair transverse momentum spectrum disagrees with the equivalent photon approach. We set limits on higher-order contributions to the cross section.
The transverse mass spectra and midrapidity yields for Xi s and Omega s are presented. For the 10% most central collisions, the Xi -bar+/h- ratio increases from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies while the Xi -/h- stays approximately constant. A hydrodynamically inspired model fit to the Xi spectra, which assumes a thermalized source, seems to indicate that these multistrange particles experience a significant transverse flow effect, but are emitted when the system is hotter and the flow is smaller than values obtained from a combined fit to pi , K, p, and Lambda s.
The pseudorapidity asymmetry and centrality dependence of charged hadron spectra in d+Au collisions at sqrt[sNN ]=200 GeV are presented. The charged particle density at midrapidity, its pseudorapidity asymmetry, and centrality dependence are reasonably reproduced by a multiphase transport model, by HIJING, and by the latest calculations in a saturation model. Ratios of transverse momentum spectra between backward and forward pseudorapidity are above unity for pT below 5 GeV/c . The ratio of central to peripheral spectra in d+Au collisions shows enhancement at 2< pT <6 GeV/c , with a larger effect at backward rapidity than forward rapidity. Our measurements are in qualitative agreement with gluon saturation and in contrast to calculations based on incoherent multiple partonic scatterings.
The short-lived K(892)* resonance provides an efficient tool to probe properties of the hot and dense medium produced in relativistic heavy-ion collisions. We report measurements of K* in sqrt[sNN]=200GeV Au+Au and p+p collisions reconstructed via its hadronic decay channels K(892)*0-->K pi and K(892)*±-->K0S pi ± using the STAR detector at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The K*0 mass has been studied as a function of pT in minimum bias p+p and central Au+Au collisions. The K*pT spectra for minimum bias p+p interactions and for Au+Au collisions in different centralities are presented. The K*/K yield ratios for all centralities in Au+Au collisions are found to be significantly lower than the ratio in minimum bias p+p collisions, indicating the importance of hadronic interactions between chemical and kinetic freeze-outs. A significant nonzero K*0 elliptic flow (v2) is observed in Au+Au collisions and is compared to the K0S and Lambda v2. The nuclear modification factor of K* at intermediate pT is similar to that of K0S but different from Lambda . This establishes a baryon-meson effect over a mass effect in the particle production at intermediate pT (2<pT <= 4GeV/c).
Midrapidity open charm spectra from direct reconstruction of D0(D0-bar)-->K± pi ± in d+Au collisions and indirect electron-positron measurements via charm semileptonic decays in p+p and d+Au collisions at sqrt[sNN]=200 GeV are reported. The D0(D0-bar) spectrum covers a transverse momentum (pT) range of 0.1<pT<3 GeV/c, whereas the electron spectra cover a range of 1<pT<4 GeV/c. The electron spectra show approximate binary collision scaling between p+p and d+Au collisions. From these two independent analyses, the differential cross section per nucleon-nucleon binary interaction at midrapidity for open charm production from d+Au collisions at BNL RHIC is d sigma NNcc-bar/dy=0.30±0.04(stat)±0.09(syst) mb. The results are compared to theoretical calculations. Implications for charmonium results in A+A collisions are discussed.
Correlations in the hadron distributions produced in relativistic Au+Au collisions are studied in the discrete wavelet expansion method. The analysis is performed in the space of pseudorapidity (| eta | <= 1) and azimuth(full 2 pi ) in bins of transverse momentum (pt) from 0.14 <= pt <= 2.1GeV/c. In peripheral Au+Au collisions a correlation structure ascribed to minijet fragmentation is observed. It evolves with collision centrality and pt in a way not seen before, which suggests strong dissipation of minijet fragmentation in the longitudinally expanding medium.
Azimuthally sensitive Hanbury Brown-Twiss interferometry in Au+Au collisions at sqrt[sNN]=200 GeV
(2004)
We present the results of a systematic study of the shape of the pion distribution in coordinate space at freeze-out in Au+Au collisions at BNL RHIC using two-pion Hanbury Brown-Twiss (HBT) interferometry. Oscillations of the extracted HBT radii versus emission angle indicate sources elongated perpendicular to the reaction plane. The results indicate that the pressure and expansion time of the collision system are not sufficient to completely quench its initial shape.
Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (nonflow correlations). Using data for Au + Au collisions at sqrt[sNN]=130 GeV from the STAR time projection chamber, it is found that four-particle correlation analyses can reliably separate flow and nonflow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of 2. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.
We report the first observation of K*(892)0--> pi K in relativistic heavy ion collisions. The transverse momentum spectrum of (K*0+K*0)/2 from central Au+Au collisions at sqrt[sNN]=130 GeV is presented. The ratios of the K*0 yield derived from these data to the yields of negative hadrons, charged kaons, and phi mesons have been measured in central and minimum bias collisions and compared with model predictions and comparable e+e-, pp, and p-barp results. The data indicate no dramatic reduction of K*0 production in relativistic heavy ion collisions despite expected losses due to rescattering effects.
The STAR Collaboration reports the first observation of exclusive rho 0 photoproduction, AuAu-->AuAu rho 0, and rho 0 production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au [star] Au [star] rho 0, in ultraperipheral heavy-ion collisions. The rho 0 have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at sqrt[sNN]=130 GeV agree with theoretical predictions treating rho 0 production and Coulomb excitation as independent processes.
We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.
Inclusive transverse momentum distributions of charged hadrons within 0.2<pT<6.0 GeV/c have been measured over a broad range of centrality for Au+Au collisions at sqrt[sNN]=130 GeV. Hadron yields are suppressed at high pT in central collisions relative to peripheral collisions and to a nucleon-nucleon reference scaled for collision geometry. Peripheral collisions are not suppressed relative to the nucleon-nucleon reference. The suppression varies continuously at intermediate centralities. The results indicate significant nuclear medium effects on high-pT hadron production in heavy-ion collisions at high energy.
We report the first measurement of strange ( Lambda ) and antistrange ( Lambda -bar) baryon production from sqrt[sNN]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda -bar hyperons is found to be approximately proportional to the number of negative hadrons. The production of Lambda -bar hyperons relative to negative hadrons increases very rapidly with transverse momentum. The magnitude of the increase cannot be described by existing hadronic string fragmentation models alone.
Temperature- and field-dependent 1H-, 19F-, and 79,81Br-NMR measurements together with zero - field 79,81Br-NQR measurements on polycrystalline samples of barlowite, Cu4(OH)6FBr are conducted to study the magnetism and possible structural distortions on a microscopic level. The temperature dependence of the 79,81Br-NMR spin-lattice relaxation rates 1/T1 indicate a phase transition at TN ≃ 15 K which is of magnetic origin, but with an unusually weak slowing down of fluctuations below TN. Moreover, 1/T1T scales linear with the bulk susceptibility which indicates persisting spin fluctuations down to 2 K. Quadupolare resonance (NQR) studies reveal a pair of zero-field NQR- lines associated with the two isotopes of Br with the nuclear spins of I = 3/2. Quadrupole coupling constants of vQ ≃ 28.5 MHz and 24.7 MHz for 79Br- and 81Br-nuclei are determined from Br-NMR and the asymmetry parameter of the electric field gradient was estimated to η ≃ 0.2. The Br-NQR lines are consistent with our findings from Br-NMR and they are relatively broad, even above TN. This broadening and the relative large η value suggests a symmetry reduction at the Br- site reflecting the presence of a local distortion in the lattice. Our density-functional calculations show that the displacements of Cu2 atoms located between the kagome planes do not account for this relatively large η. On the other hand, full structural relaxation, including the deformation of kagome planes, leads to a better agreement with the experiment.
Two-pion correlation functions in Au+Au collisions at sqrt[sNN] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in sqrt[sNN].
The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d-bar and 3He-bar are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the 3He-bar freeze-out volume is smaller than the d-bar freeze-out volume.
We present the first measurement of midrapidity vector meson phi production in Au+Au collisions at RHIC (sqrt[sNN]=130 GeV) from the STAR detector. For the 11% highest multiplicity collisions, the slope parameter from an exponential fit to the transverse mass distribution is T=379±50(stat)±45(syst) MeV, the yield dN/dy=5.73±0.37(stat)±0.69(syst) per event, and the ratio N phi /Nh- is found to be 0.021±0.001(stat)±0.004(syst). The measured ratio N phi /Nh- and T for the phi meson at midrapidity do not change for the selected multiplicity bins.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Ausgehend von der Beobachtung, dass ökologische Fragen in Comics eine zunehmende Rolle spielen, liefert der Beitrag einen systematisierenden Einblick in den Variantenreichtum graphischer Umwelt- und Klimawandelliteratur und untersucht, auf welche Art und Weise Helden hier inszeniert werden. Dabei wird erkennbar, dass die Kritik an einer globalen Umweltkrise nicht nur im Rahmen der Handlung, sondern insbesondere durch erzählerische Mittel und Aspekte der Figurendarstellung vermittelt wird.
The risk of developing severe complications from an influenza virus infection is increased in patients with chronic inflammatory diseases such as psoriasis (PsO) and atopic dermatitis (AD). However, low influenza vaccination rates have been reported. The aim of this study was to determine vaccination rates in PsO compared to AD patients and explore patient perceptions of vaccination. A multicenter cross-sectional study was performed in 327 and 98 adult patients with PsO and AD, respectively. Data on vaccination, patient and disease characteristics, comorbidity, and patient perceptions was collected with a questionnaire. Medical records and vaccination certificates were reviewed. A total of 49.8% of PsO and 32.7% of AD patients were vaccinated at some point, while in season 2018/2019, 30.9% and 13.3% received an influenza vaccination, respectively. There were 96.6% and 77.6% of PsO and AD patients who had an indication for influenza vaccination due to age, immunosuppressive therapy, comorbidity, occupation, and/or pregnancy. Multivariate regression analysis revealed higher age (p < 0.001) and a history of bronchitis (p = 0.023) as significant predictors of influenza vaccination in PsO patients. Considering that most patients had an indication for influenza vaccination, the rate of vaccinated patients was inadequately low.
Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases
(2016)
Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A. Simultaneous VEGF-A and ANG-2 inhibition was found to reduce vessel lesion number, permeability, retinal edema, and neuron loss more effectively than either agent alone in a spontaneous choroidal neovascularization (CNV) model. We describe the generation of a bispecific domain-exchanged (crossed) monoclonal antibody (CrossMAb; RG7716) capable of binding, neutralizing, and depleting VEGF-A and ANG-2. RG7716 showed greater efficacy than anti-VEGF-A alone in a non-human primate laser-induced CNV model after intravitreal delivery. Modification of RG7716’s FcRn and FccR binding sites disabled the antibodies’ Fc-mediated effector functions. This resulted in increased systemic, but not ocular, clearance. These properties make RG7716 a potential nextgeneration therapy for neovascular indications of the eye.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.
The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h-) in Au+Au interactions at sqrt[sNN] = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dNh-/d eta | eta = 0 = 280±1(stat)±20(syst), an increase per participant of 38% relative to pp-bar collisions at the same energy. The mean transverse momentum is 0.508±0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h- yield per participant is a strong function of pperp. The pseudorapidity distribution is almost constant within | eta |<1.
We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25<pperp<0.95 GeV/c are found to fall less steeply for more central collisions. The extrapolated antiproton rapidity density is found to scale approximately with the negative hadron multiplicity density.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[sNN] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of | y|<0.5 and 0.4<pt<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65±0.01(stat)±0.07(syst) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p-bar pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.
Molecular and cellular research modalities for the study of liver pathologies have been tremendously improved over the recent decades. Advanced technologies offer novel opportunities to establish cell isolation techniques with excellent purity, paving the path for 2D and 3D microscopy and high-throughput assays (e.g., bulk or single-cell RNA sequencing). The use of stem cell and organoid research will help to decipher the pathophysiology of liver diseases and the interaction between various parenchymal and non-parenchymal liver cells. Furthermore, sophisticated animal models of liver disease allow for the in vivo assessment of fibrogenesis, portal hypertension and hepatocellular carcinoma (HCC) and for the preclinical testing of therapeutic strategies. The purpose of this review is to portray in detail novel in vitro and in vivo methods for the study of liver cell biology that had been presented at the workshop of the 8th meeting of the European Club for Liver Cell Biology (ECLCB-8) in October of 2018 in Bonn, Germany.
Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.
ß-Hydroxybutyrate (BHB) is a ketone body formed in high amounts during lipolysis and fasting. Ketone bodies and the ketogenic diet were suggested as neuroprotective agents in neurodegenerative disease. In the present work, we induced transient ischemia in mouse brain by unilaterally occluding the middle cerebral artery for 90 min. BHB (30 mg/kg), given immediately after reperfusion, significantly improved the neurological score determined after 24 h. In isolated mitochondria from mouse brain, oxygen consumption by the complexes I, II and IV was reduced immediately after ischemia but recovered slowly over 1 week. The single acute BHB administration after reperfusion improved complex I and II activity after 24 h while no significant effects were seen at later time points. After 24 h, plasma and brain BHB concentrations were strongly increased while mitochondrial intermediates (citrate, succinate) were unchanged in brain tissue. Our data suggest that a single administration of BHB may improve mitochondrial respiration for 1–2 days but not for later time points. Endogenous BHB formation seems to complement the effects of exogenous BHB administration.
Transfer RNA fragments replace microRNA regulators of the cholinergic post-stroke immune blockade
(2020)
Stroke is a leading cause of death and disability. Recovery depends on a delicate balance between inflammatory responses and immune suppression, tipping the scale between brain protection and susceptibility to infection. Peripheral cholinergic blockade of immune reactions fine-tunes this immune response, but its molecular regulators are unknown. Here, we report a regulatory shift in small RNA types in patient blood sequenced two days after ischemic stroke, comprising massive decreases of microRNA levels and concomitant increases of transfer RNA fragments (tRFs) targeting cholinergic transcripts. Electrophoresis-based size-selection followed by RT-qPCR validated the top 6 upregulated tRFs in a separate cohort of stroke patients, and independent datasets of small and long RNA sequencing pinpointed immune cell subsets pivotal to these responses, implicating CD14+ monocytes in the cholinergic inflammatory reflex. In-depth small RNA targeting analyses revealed the most-perturbed pathways following stroke and implied a structural dichotomy between microRNA and tRF target sets. Furthermore, lipopolysaccharide stimulation of murine RAW 264.7 cells and human CD14+ monocytes upregulated the top 6 stroke-perturbed tRFs, and overexpression of stroke-inducible tRF-22-WE8SPOX52 using an ssRNA mimic induced downregulation of immune regulator Z-DNA binding protein 1 (Zbp1). In summary, we identified a “changing of the guards” between RNA types that may systemically affect homeostasis in post-stroke immune responses, and pinpointed multiple affected pathways, which opens new venues for establishing therapeutics and biomarkers at the protein- and RNA-level.
Significance Statement Ischemic stroke triggers peripheral immunosuppression, increasing the susceptibility to post-stroke pneumonia that is linked with poor survival. The post-stroke brain initiates intensive communication with the immune system, and acetylcholine contributes to these messages; but the responsible molecules are yet unknown. We discovered a “changing of the guards,” where microRNA levels decreased but small transfer RNA fragments (tRFs) increased in post-stroke blood. This molecular switch may re-balance acetylcholine signaling in CD14+ monocytes by regulating their gene expression and modulating post-stroke immunity. Our observations point out to tRFs as molecular regulators of post-stroke immune responses that may be potential therapeutic targets.
Transfer RNA fragments replace microRNA regulators of the cholinergic poststroke immune blockade
(2020)
Stroke is a leading cause of death and disability. Recovery depends on a delicate balance between inflammatory responses and immune suppression, tipping the scale between brain protection and susceptibility to infection. Peripheral cholinergic blockade of immune reactions fine-tunes this immune response, but its molecular regulators are unknown. Here, we report a regulatory shift in small RNA types in patient blood sequenced 2 d after ischemic stroke, comprising massive decreases of microRNA levels and concomitant increases of transfer RNA fragments (tRFs) targeting cholinergic transcripts. Electrophoresis-based size-selection followed by qRT-PCR validated the top six up-regulated tRFs in a separate cohort of stroke patients, and independent datasets of small and long RNA sequencing pinpointed immune cell subsets pivotal to these responses, implicating CD14+ monocytes in the cholinergic inflammatory reflex. In-depth small RNA targeting analyses revealed the most-perturbed pathways following stroke and implied a structural dichotomy between microRNA and tRF target sets. Furthermore, lipopolysaccharide stimulation of murine RAW 264.7 cells and human CD14+ monocytes up-regulated the top six stroke-perturbed tRFs, and overexpression of stroke-inducible tRF-22-WE8SPOX52 using a single-stranded RNA mimic induced down-regulation of immune regulator Z-DNA binding protein 1. In summary, we identified a “changing of the guards” between small RNA types that may systemically affect homeostasis in poststroke immune responses, and pinpointed multiple affected pathways, which opens new venues for establishing therapeutics and biomarkers at the protein and RNA level.
Background: About 2000 children and adolescents under the age of 18 are diagnosed with cancer each year in Germany. Because of current medical treatment methods, a high survival rate can be reached for many types of the disease. Nevertheless, patients face a number of long-term effects related to the treatment. As a result, physical and psychological consequences have increasingly become the focus of research in recent years. Social dimensions of health have received little attention in health services research in oncology so far. Yet, there are no robust results that allow an estimation of whether and to what extent the disease and treatment impair the participation of children and adolescents and which factors mediate this effect. Social participation is of great importance especially because interactions with peers and experiences in different areas of life are essential for the development of children and adolescents.
Methods: Data are collected in a longitudinal, prospective, observational multicenter study. For this purpose, all patients and their parents who are being treated for cancer in one of the participating clinics throughout Germany will be interviewed within the first month after diagnosis (t1), after completion of intensive treatment (t2) and half a year after the end of intensive treatment (t3) using standardized questionnaires. Analysis will be done by descriptive and multivariate methods.
Discussion: The results can be used to identify children and adolescents in high-risk situations at an early stage in order to be able to initiate interventions tailored to the needs. Such tailored interventions will finally reduce the risk of impairments in the participation of children and adolescents and increase quality of life.
Trial registration: ClinicalTrials.gov: NCT04101123.
Objective: We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. Methods: A web-based questionnaire was e-mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. Results: A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38–0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00–2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46–34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (95% CI = 1.22–10.65) for females compared to non-females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. Interpretation: Given an incidence of 0.02 to 0.15 per 100,000 person-months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women.
Longitudinal changes of cortical microstructure in Parkinson's disease assessed with T1 relaxometry
(2016)
Background: Histological evidence suggests that pathology in Parkinson's disease (PD) goes beyond nigrostriatal degeneration and also affects the cerebral cortex. Quantitative MRI (qMRI) techniques allow the assessment of changes in brain tissue composition. However, the development and pattern of disease-related cortical changes have not yet been demonstrated in PD with qMRI methods. The aim of this study was to investigate longitudinal cortical microstructural changes in PD with quantitative T1 relaxometry.
Methods: 13 patients with mild to moderate PD and 20 matched healthy subjects underwent high resolution T1 mapping at two time points with an interval of 6.4 years (healthy subjects: 6.5 years). Data from two healthy subjects had to be excluded due to MRI artifacts. Surface-based analysis of cortical T1 values was performed with the FreeSurfer toolbox.
Results: In PD patients, a widespread decrease of cortical T1 was detected during follow-up which affected large parts of the temporo-parietal and occipital cortices and also frontal areas. In contrast, age-related T1 decrease in the healthy control group was much less pronounced and only found in lateral frontal, parietal and temporal areas. Average cortical T1 values did not differ between the groups at baseline (p = 0.17), but were reduced in patients at follow-up (p = 0.0004). Annualized relative changes of cortical T1 were higher in patients vs. healthy subjects (patients: − 0.72 ± 0.64%/year; healthy subjects: − 0.17 ± 0.41%/year, p = 0.007).
Conclusions: In patients with PD, the development of widespread changes in cortical microstructure was observed as reflected by a reduction of cortical T1. The pattern of T1 decrease in PD patients exceeded the normal T1 decrease as found in physiological aging and showed considerable overlap with the pattern of cortical thinning demonstrated in previous PD studies. Therefore, cortical T1 might be a promising additional imaging marker for future longitudinal PD studies. The biological mechanisms underlying cortical T1 reductions remain to be further elucidated.
Herausforderungen meistern, Krisen überwinden : über Ratgeberliteratur aus narratologischer Sicht
(2012)
Ratgebende Texte sind eine feste Größe im Buchmarkt. Ausweislich des Branchenmonitors des Börsenvereins des deutschen Buchhandels zählte im Jahr 2010 jedes siebte in Deutschland verkaufte Buch zum Marktsegment Ratgeber – im ersten Halbjahr 2011 sogar fast jedes sechste. Wenn im Folgenden der Frage nachgegangen werden soll, auf welche Art und Weise in diesen weit verbreiteten Texten Ratschläge an den Leser gebracht werden, welche Erzählstrukturen und -strategien auszumachen sind und welche Bedeutung ihnen zukommt, dann ist zunächst festzuhalten, dass Ratgeber aus mehreren Textsorten zusammengesetzt und zumeist nicht dominant erzählerisch angelegt sind – 'erzählerisch' in dem Sinne, dass ein Geschehen vergegenwärtigt wird. Vielmehr werden erzählende mit informativen, argumentativen, essayistischen und beschreibenden Passagen kombiniert. Ratgeberliteratur wird hier als Sammelbezeichnung für die als gedruckte Bücher vorliegenden Ratgeber (gegenüber Ratgebertexten in anderen Medien wie Zeitschriften, Filmen oder Internetforen) verstanden. Der Terminus Ratgeberliteratur zielt also auf eine mediale Spezifikation.
Erzählen ist eine grundlegende Form unseres Zugriffs auf Wirklichkeit. In den verschiedensten Bereichen der alltäglichen Lebenswelt und nicht zuletzt auf den Gebieten wissenschaftlicher Erkenntnis orientieren und verständigen wir uns mit Hilfe von Erzählungen. Reportagen des investigativen Journalismus, Selbstdarstellungen von Politikern im Wahlkampf, Erlebnisberichte in Internetblogs, Anamnesen im medizinischen Patientengespräch, Plädoyers vor Gericht, Vermittlungen von Verhaltensnormen in populärer Ratgeberliteratur, Heilserzählungen im Gottesdienst, Fallgeschichten in juristischen Lehrbüchern, ökonomische Prognosen von Kursverläufen – all diese Kommunikationen erfolgen wesentlich in erzählender Form. Anders als in den erfundenen Geschichten der Literatur bezieht man sich in diesen Erzählungen direkt auf unsere konkrete Wirklichkeit und trifft Aussagen mit einem spezifischen Geltungsanspruch: 'So ist es (gewesen)'. Solche Erzählungen mit unmittelbarem Bezug auf die konkrete außersprachliche Realität nennen wir Wirklichkeitserzählungen. In den vergangenen Jahrzehnten wurde die referentielle Leistung sprachlicher Kommunikation im Zeichen strukturalistischer und poststrukturalistischer Theorien allzu oft zugunsten eines pauschalen 'Panfiktionalismus' unterschlagen. Zweifellos 'konstruieren' Wirklichkeitserzählungen in erheblichem Maße eine Realität; aber sie sind eben auch auf eine intersubjektiv gegebene Wirklichkeit bezogen. Wirklichkeitserzählungen sind sowohl konstruktiv als auch referentiell – darin liegt ihre besondere erkenntnistheoretische Bedeutung. Es gilt, den referentiellen Aspekt von Wirklichkeitserzählungen angemessen zu berücksichtigen, ohne deren konstruktive Elemente zu vernachlässigen.
Micky Maus, Superman, Asterix, Popeye - zahlreiche Figuren aus Comics haben ein Eigenleben entwickelt und sich als Marke etabliert. Die Figuren halten die Fortsetzungsgeschichten zusammen und stellen entsprechend einen Wiedererkennungswert dar. Vor diesem Hintergrund ist es bemerkenswert, dass sich die inzwischen doch einigermaßen etablierte Comic-Forschung der Betrachtung der Figuren nur am Rande gewidmet hat. Das gilt erst recht für jene Sonderform des Comics, die im Folgenden in den Fokus gerückt werden soll: die Graphic Novel.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Purpose: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS.
Materials and Methods: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and correlation with disability was investigated for regions exhibiting significant group differences.
Results: PD was increased in the whole GM, cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was prolonged and correlated with disability in the whole GM and cerebral cortex.
Conclusion: Our study suggests that the qMRI parameters GM PD (which likely indicates replacement of neural tissue with water) and cortical T1 (which reflects cortical damage including and beyond increased water content) are promising qMRI candidates for the assessment of disease status, and are related to disability in SPMS.
The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.
Monoklonale Antikörper und rekombinante Antikörperfragmente gegen sekundäre Arzneipflanzenmetabolite
(2004)
Monoklonale Antikörper sind seit vielen Jahren aus den biochemischen und molekularbiologischen Laboratorien nicht mehr wegzudenken. Sowohl in der Grundlagenforschung, als auch in der angewandten medizinischen Diagnostik und der Therapie spielen sie eine immer wichtigere Rolle. Dennoch konnten sich monoklonale Antikörper als Hilfsmittel im Bereich der Naturstoffanalytik bisher noch nicht durchsetzen. Im Mittelpunkt dieser Arbeit stand daher die Frage, inwieweit sich monoklonale Antikörper und rekombinante Antikörperfragmente für die Analytik komplexer Naturstoffgemische eignen. Eine der Zielstrukturen, gegen die monoklonale Antikörper generiert werden sollten, ist das pentazyklische Triterpen Oleanolsäure. Oleanolsäure ist als Aglykon in zahlreichen verschiedenen Triterpensaponinen enthalten. Triterpensaponine bzw. Triterpensaponin-haltige Arzneipflanzen spielen aufgrund ihres breiten Wirkungsspektrums in der Phytotherapie eine wichtige Rolle. Sie zeichnen sich nachweislich durch venentonisierende, antiödematöse, antiphlogistische, diuretische, expektorierende und broncholytische Eigenschaften aus. Da es sich bei den Triterpensaponinen um eine sehr heterogene Stoffgruppe handelt, ist ihre Analytik sehr aufwendig. Monoklonale Antikörper könnten daher bei der Analytik von komplexen Saponingemischen sehr nützlich sein. In Zusammenarbeit mit Frau Dr. Kerstin Brand aus dem Arbeitskreis von PD Dr. Werner Knöss (Universität Bonn) konnten verschiedene monoklonale Antikörper gegen Oleanolsäure etabliert werden. Im Rahmen dieser Dissertation wurden die Bindungseigenschaften dieser Antikörper eingehend charakterisiert. In kompetitiven ELISAs konnten die Molekülepitope, an die die verschiedenen Antikörper binden, bestimmt werden. Außerdem wurden die Immunglobuline auf Kreuzreaktivitäten gegenüber 72 unterschiedlichen sekundären Arzneipflanzenmetaboliten untersucht. Die monoklonalen Antikörper zeigten dabei keine Interaktion mit Steroiden, Phytosterolen und Herzglykosiden – Substanzen die zwar in die Gruppe der Triterpene eingeordnet werden können, sich aber in ihrer Struktur und Stereochemie deutlich von der Oleanolsäure unterscheiden. Gegenüber zahlreichen pentazyklischen Triterpenen, die strukturelle Ähnlichkeiten mit der Oleanolsäure besitzen, zeigten hingegen alle untersuchten Immunglobuline eine ausgeprägte Kreuzreaktivität. Daher eignen sie sich für die Analytik von komplex zusammengesetzten Triterpengemischen, z.B. von Arzneipflanzenextrakten. Dies konnte durch verschiedene direkte und indirekte Kompetitionsversuche mit unterschiedlichen Arzneipflanzenextrakten im Rahmen dieser Arbeit und der Dissertation von Frau Dr. Kerstin Brand gezeigt werden. Mit Hilfe eines kompetitiven ELISAs ist z.B. ein Screening von unbekannten Arzneipflanzen auf Triterpensaponine möglich. Auch eine Wertbestimmung von Arzneipflanzen oder Arzneipflanzenextrakten mit Hilfe der monoklonalen Antikörper ist denkbar, sofern eine Referenz zur Verfügung steht, auf den die Kompetitionsergebnisse bezogen werden können. Der Einsatz der hier vorgestellten Antikörper wird allerdings dadurch eingeschränkt, dass die Immunglobuline eine unvorhersehbare Polyspezifität gegenüber den polyphenolischen Sekundärmetaboliten Quercetin und Ellagsäure zeigten. Bei einem Einsatz der Antikörper im Rahmen der Naturstoffanalytik sind daher Vorversuche erforderlich, um diese Substanzen zu identifizieren und wenn möglich zu entfernen. Einer der untersuchten monoklonalen Antikörper, der Antikörper der Zelllinie 10F10, zeigte eine Kreuzreaktivität gegenüber verschiedenen ß-Boswelliasäuren. Boswelliasäuren sind in der Lage, das Enzym 5-Lipoxygenase zu hemmen und dadurch die Synthese von entzündungsfördernden Leukotrienen zu inhibieren. Daher scheinen Boswelliasäuren viel versprechende Arzneistoffe bei der Therapie der unterschiedlichsten inflammatorischen Erkrankungen, wie z.B. Colitis ulcerosa, Morbus Crohn, Asthma bronchiale oder rheumatoider Arthritis zu sein. Der Antikörper der Zelllinie 10F10 soll im Arbeitskreis von Prof. Dieter Steinhilber am Institut für Pharmazeutische Chemie der Universität Frankfurt unter anderem für eine Immobilisierung der Boswelliasäuren an Immunaffinitätssäulen eingesetzt werden. In diesem Arbeitskreis wird der Einfluss von ß-Boswelliasäuren auf die 5-Lipoxygenase intensiv erforscht. In einem zweiten Projekt wurden rekombinante scFv-Antikörperfragmente gegen das Triterpen Oleanolsäure und gegen das Pyrrolizidinalkaloid Retrorsin generiert. Pyrrolizidinalkaloide sind hepatotoxische Sekundärmetabolite, die in zahlreichen Nutzpflanzen und traditionellen Arzneipflanzen enthalten sind. Insgesamt wurden vier verschiedene scFv-Fragmente konstruiert. Zwei Anti- Oleanolsäure-Antikörperfragmente konnten in E. coli erfolgreich periplasmatisch exprimiert und ihre Funktionalität in verschiedenen Antigenbindungsstudien nachgewiesen werden. Darüber hinaus wurde eine Phagen-Display- und Phagen- Panning-Methode etabliert, mit deren Hilfe es möglich ist, gezielt nach funktionellen Antikörperfragmenten zu suchen. Mit dieser Methode sollte es möglich sein, nach erfolgter Mutation der verschiedenen scFv-Fragmente, Proteine mit neuen Bindungseigenschaften zu identifizieren. Interessant wären dabei z.B. scFv- Fragmente, die mit Pyrrolizidin-N-oxiden interagieren. Gegen diese Substanzen konnten im Arbeitskreis Dingermann mit Hilfe der konventionellen Hybridoma- Technologie bisher noch keine monoklonalen Antikörper generiert werden. Im Rahmen dieser Arbeit konnte gezeigt werden, dass es sich bei monoklonalen Antikörpern und rekombinanten Antikörperfragmenten um interessante Hilfsstoffe für die Naturstoffanalytik handelt, deren Bedeutung für dieses Anwendungsgebiet aber bisher noch deutlich unterbewertet ist. Es wäre daher sehr interessant, die hier vorgestellten Projekte fortzuführen und die Arbeitsmethoden weiter zu optimieren. Mit den im Rahmen dieser Arbeit charakterisierten Anti-Oleanolsäure-Antikörpern stehen bereits drei Immunglobuline für die Arzneipflanzenanalytik zur Verfügung. Von allen drei Antikörpern liegen inzwischen auch scFv-Fragmente vor. Diese Fragmente könnten modifiziert und mit Hilfe der hier vorgestellten Phagen-Display-Methode nach Proteinen mit modifizierten Bindungseigenschaften gesucht werden. Letztendlich wäre auf diese Weise die Generierung eines großen Sortiments von Antikörpern und Antikörperfragmenten für die Analytik der unterschiedlichsten Substanzklassen möglich.
Transfer RNA fragments replace microRNA regulators of the cholinergic post-stroke immune blockade
(2020)
Stroke is a leading cause of death and disability. Recovery depends on balance between inflammatory response and immune suppression, which can be CNS-protective but may worsen prognosis by increasing patients’ susceptibility to infections. Peripheral cholinergic blockade of immune reactions fine-tunes this immune response, but its molecular regulators are unknown. Therefore, we sought small RNA balancers of the cholinergic anti-inflammatory pathway in peripheral blood from ischemic stroke patients. Using RNA-sequencing and RT-qPCR, we discovered in patients’ blood on day 2 after stroke a “change of guards” reflected in massive decreases in microRNAs (miRs) and increases in transfer RNA fragments (tRFs) targeting cholinergic transcripts. Electrophoresis-based size-selection followed by RT-qPCR validated the top 6 upregulated tRFs in a separate cohort of stroke patients, and independent small RNA-sequencing datasets presented post-stroke enriched tRFs as originating from lymphocytes and monocytes. In these immune compartments, we found CD14+ monocytes to express the highest amounts of cholinergic transcripts. In-depth analysis of CD14+ regulatory circuits revealed minimally overlapping subsets of transcription factors carrying complementary motifs to miRs or tRFs, indicating different roles for the stroke-perturbed members of these small RNA species. Furthermore, LPS-stimulated murine RAW264.7 cells presented dexamethasone-suppressible upregulation of the top 6 tRFs identified in human patients, indicating an evolutionarily conserved and pharmaceutically treatable tRF response to inflammatory cues. Our findings identify tRF/miR subgroups which may co-modulate the homeostatic response to stroke in patients’ blood and open novel venues for establishing RNA-targeted concepts for post-stroke diagnosis and therapeutics.
The results from the STAR Collaboration on directed flow (v1), elliptic flow (v2), and the fourth harmonic (v4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrt[sNN]=200GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a blast-wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v2, scaling with the number of constituent quarks and parton coalescence are discussed. For v4, scaling with v22 and quark coalescence are discussed.
Glucose hypometabolism, mitochondrial dysfunction, and cholinergic deficits have been reported in early stages of Alzheimer’s disease (AD). Here, we examine these parameters in TgF344-AD rats, an Alzheimer model that carries amyloid precursor protein and presenilin-1 mutations, and of wild type F344 rats. In mitochondria isolated from rat hippocampi, we found reductions of complex I and oxidative phosphorylation in transgenic rats. Further impairments, also of complex II, were observed in aged (wild-type and transgenic) rats. Treatment with a “cocktail” containing magnesium orotate, benfotiamine, folic acid, cyanocobalamin, and cholecalciferol did not affect mitochondrial activities in wild-type rats but restored diminished activities in transgenic rats to wild-type levels. Glucose, lactate, and pyruvate levels were unchanged by age, genetic background, or treatment. Using microdialysis, we also investigated extracellular concentrations of acetylcholine that were strongly reduced in transgenic animals. Again, ACh levels in wild-type rats did not change upon treatment with nutrients, whereas the cocktail increased hippocampal acetylcholine levels under physiological stimulation. We conclude that TgF344-AD rats display a distinct mitochondrial and cholinergic dysfunction not unlike the findings in patients suffering from AD. This dysfunction can be partially corrected by the application of the “cocktail” which is particularly active in aged rats. We suggest that the TgF344-AD rat is a promising model to further investigate mitochondrial and cholinergic dysfunction and potential treatment approaches for AD.
We present a systematic analysis of two-pion interferometry in Au+Au collisions at sqrt[sNN]=200GeV using the STAR detector at Relativistic Heavy Ion Collider. We extract the Hanbury-Brown and Twiss radii and study their multiplicity, transverse momentum, and azimuthal angle dependence. The Gaussianness of the correlation function is studied. Estimates of the geometrical and dynamical structure of the freeze-out source are extracted by fits with blast-wave parametrizations. The expansion of the source and its relation with the initial energy density distribution is studied.