julilili42/papers huggingface dataset:
Protective Effects of Intranasal Losartan in the APP/PS1 Transgenic Mouse Model of Alzheimer Disease
2010-04-01

The local renin–angiotensin system (RAS) in the brain is a multitasking system controlling a plethora of essential functions such as neurogenic hypertension, baroreflexes, and sympathetic activity. Aside from its vasoactive actions, brain angiotensin II (AT-II) has also been implicated in the pathogenesis of cognitive decline, and beneficial effects of angiotensin receptor blockers (ARBs) in Alzheimer (AD) and Parkinson diseases (PD) are suggested. However, the use of ARBs at antihypertensive dosages would lead to unwanted hypotensive reactions in AD patients. Here we treated the APP/PS1 transgenic mouse model of AD with the ARB losartan (10 mg/kg body weight) to determine whether blockade of the AT-II receptor subtype 1 (AT1-R) with intranasal losartan, using at a dosage far below its systemic antihypertensive dose, could maintain its neuroprotective effects independent of its systemic vasoactive action. Intranasal losartan treatment (10 mg/kg every other day for 2 months) of APP/PS1 mice decreased amyloid β (Aβ) plaques 3.7-fold. Blood serum levels of interleukin-12 (IL-12)p40/p70, IL-1β, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in the vehicle-treated APP/PS1 mice. Intranasal losartan not only decreased IL-12p40/p70, IL-1β, and GM-CSF, but also increased IL-10, which suppresses inflammation. Furthermore, losartan markedly increased tyrosine hydroxylase expression in the striatum and locus coeruleus. In conclusion, losartan exerts direct neuroprotective effects via its Aβ-reducing and antiinflammatory effects in the central nervous system (CNS). Therefore, intranasal losartan and potentially other ARBs, at concentrations below their threshold for altering systemic blood pressure, offer a new approach for the treatment of AD.
Cognitive Function and Sleep Related Breathing Disorders in a Healthy Elderly Population: the Synapse Study
2010-04-01

The impact of undiagnosed SRBD on cognitive function appeared quite limited in a generally older healthy population, and only slightly affected severe cases. The implication of undiagnosed SRBD on the cognitive impairment in elderly subjects remains hypothetical and needs to be prospectively studied.
The Mechanism of the Einstellung (Set) Effect
2010-04-01

The eye movements of expert players trying to solve a chess problem show that the first idea that comes to mind directs attention toward sources of information consistent with it and away from inconsistent information. This bias continues unconsciously even when players believe they are looking for alternatives. The result is that alternatives to the first idea are ignored. This mechanism for biasing attention ensures a speedy response in familiar situations, but it can lead to errors when the first thought that comes to mind is not appropriate. We propose that this mechanism is the source of many cognitive biases, from phenomena in problem solving and reasoning to perceptual errors and failures in memory.
The thermochronological record of tectonic and surface process interaction at the Yakutat-North American collision zone in southeast Alaska
2010-04-01

We investigate the material fluxes in space and time as a result of exhumation and erosion processes at the ongoing Yakutat--North American collision in southeast Alaska. Many thermochronologic studies using a variety of sampling strategies are challenged by the widespread ice cover that limit field observations and accessibility. This paper reviews new and published low-temperature thermochronological data from southeast Alaska to give a comprehensive interpretation of the exhumation patterns through time and how they are influenced by surface processes and climate change. We find that the southeastern margin of Alaska was exhumed and eroded long before the late Miocene--Pliocene Yakutat collision, but since the beginning of the subduction of the Yakutat lithosphere in the Oligocene/early Miocene. Today there is a distinct pattern of exhumation in southeast Alaska with a localized very rapid and deep-seated exhumation at the Yakutat plate corner (St. Elias syntaxis), where strike slip motion changes to convergence. Exhumation is also rapid, but less deep along the dextral Fairweather fault, and in the evolving fold and thrust belt. We present a re-interpretation of the exhumation pattern in the fold and thrust belt and suggest that mass transport by exhumation is parallel to the observed active thrust faults and oblique to the suture zone and orogenic strike. The locus of most rapid exhumation migrated from northwest to southeast with Recent exhumation occurring near the St. Elias syntaxis. Exhumation of the Chugach terrane rocks is still active, however to a lesser degree than on the south side of the orogen where precipitation rates are much higher. The Wrangellia terrane to the north has experienced little exhumation and has essentially formed the backstop for terrane accretion in southeast Alaska since the Early Cretaceous. Apatite U-Th/He ages give the first evidence that rocks of the Wrangell Range have only been recently uplifted and eroded as a consequence of the continuing Yakutat collision. In general the thermochronology in southeast Alaska reveals that climate variations across the region as well as changes through time have a limited influence on the pattern of erosion and that the location of deep exhumation is primarily influenced by tectonic processes.
Chiral iridium(I) bis(NHC) complexes as catalysts for asymmetric transfer hydrogenation
2010-04-01

Abstract The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N ‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L ‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N ‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Compositional variation of the tennantite–tetrahedrite solid-solution series in the Schwarzwald ore district (SW Germany): The role of mineralization processes and fluid source
2010-04-01

Abstract The study presents analysis from members of the tennantite–tetrahedrite solid-solution series (‘fahlore’) from 78 locations in the Schwarzwald ore district of SW Germany. Electron microprobe analysis is used to correlate the compositional variations of the fahlores with mineral association, host rock, tectonic history and precipitation mechanisms. Results indicate that most fahlores from gneiss-hosted veins do not have distinctive geochemical characteristics and range from tetrahedrite to tennantite end-member composition with variable trace-element content. However, diagenetically formed fahlore has a near-end-member tennantite composition with very small trace-element content. Red-bed-hosted fahlore formed by fluid mixing is tennantite enriched in Hg that probably has its source in the red-bed sediments. Fahlore formed from granite-related late-magmatic fluids, or from mixing of fluids of which one has equilibrated with granitic basement rocks, is typically As- and Bi-rich (up to 22.2 wt.% Bi). Gneiss-hosted fahlore formed by fluid cooling is Ag-rich near-end-member tetrahedrite. Some fahlores reflect their paragenetic association, e.g. a large Ag content in association with Ag-bearing minerals or a large Co and Ni in association with Co- and Ni-arsenides. Although they have similar compositions, gneiss-hosted fahlores show systematic variations in Ag contents and Fe/Zn ratios between the Central and the Southern Schwarzwald with Fe-rich fahlore in higher stratigraphic levels (North) and Zn- and Ag-rich fahlore in lower stratigraphic levels (South). We show that fahlore composition varies with precipitation mechanism (cooling vs . mixing vs . diagenesis), depth of formation, paragenetic association and host rock. Comparison with fahlores from other European occurrences indicates that these conclusions are consistent with fahlore systematics found elsewhere, and could be used to infer details of ore-forming processes.
Phase-based non-rigid registration of myocardial perfusion MRI image sequences
2010-04-01

The condition of the heart muscle tissue can be inferred by analyzing the time-intensity curves obtained with myocardial perfusion MRI. Specifically, identifying tissue that is under-supplied with blood is important when choosing a suitable therapy for patients with coronary heart disease. Before an analysis can be carried out, the images must be registered to compensate for cardiac and respiratory motion. This is a difficult problem, as the motion is non-rigid and because the image contrast varies strongly over time due to the injection of a contrast agent into the blood stream. To address these problems, an automatic non-rigid registration approach is presented that utilizes local phase instead of intensity or gradient information.
A checklist of the water mites of France (Acari: Hydrachnidia)
2010-04-01

A review is given of all species reported from France. In total, 420 species and seven subspecies have been found in France. The following synonyms are established: Atractides vandeli Angelier, Decamps and Rey as a synonym of A. phreaticus Motas and Tanasachi, Atractides fonticolus gallicus Angelier, Decamps and Rey as a synonym of A. spinipes Koch and Barbaxonella pilosa Angelier, Decamps and Rey as a synonym of B. angulata (K. Viets). The following species are reported for the first time: Atractides orghidani Motas and Tanasachi, Hydrachna goldfeldi Thor, Hydrodroma pilosa Besseling, Limnesia curvipalpis Tuzovskij, Limnesia undulatoides Davids, Piona ambigua (Piersig), Forelia curvipalpis K. Viets, Mideopsis roztoczensis Biesiadka and Kowalik, Arrenurus octagonus Halbert and Arrenurus tubulator (Muller). Moreover, Arrenurus affinis Koenike is reported for the first time with certainty. For each species, all references are given which contain geographical information about their occurrence in France. Numerous new records are given, especially of species from standing waters.
Abstract 2396: IMA950: A novel multi-peptide cancer vaccine for treatment of glioblastoma
2010-04-01

Abstract Despite promising results of various therapeutic approaches currently under investigation, including active immunotherapy, glioblastoma (GBM) remains one of the most fatal tumor types. IMA950 is a novel peptide vaccine aiming at the induction of a broad T-cell response against a variety of tumor-relevant antigens expressed by GBM cells. IMA950 consists of 11 synthetic tumor-associated peptides (TUMAPs) isolated from more than 30 primary human GBM specimens. Nine of the TUMAPs bind to the human leukocyte antigen (HLA) class I allele A*02 expressed by ∼ 45% of the Caucasian population and two TUMAPs bind to various HLA class II (DR) alleles expressed by the majority of patients. Therefore, cytotoxic T-lymphocyte (CTL) as well as T helper (Th) responses are expected to arise from vaccination with IMA950. TUMAPs were identified by isolating HLA-peptide complexes from primary tumors and determining the peptide sequences by mass spectrometry. This analysis resulted in the identification of more than 3,000 different HLA-A*02 peptides expressed by one or more GBM samples. TUMAPs were ranked according to a variety of criteria, including mRNA over-expression of the source antigens in GBM compared with normal tissues, known relevance of the source antigens in oncogenic processes, frequency of expression in GBM samples, in vitro immunogenicity in healthy donors, and feasibility of pharmaceutical development. Based on this approach IMA950 has been composed of 11 TUMAPs derived from 10 different source antigens ranking high in these categories. “Over-presentation” of finally selected TUMAPs was confirmed directly at the peptide level using a novel approach allowing label-free HLA-peptide quantitation directly by mass spectrometry. Moreover, T-cell reactivity in glioma patients was analyzed for all HLA-A*02 peptides in vitro with all patients tested responding to several IMA950 TUMAPs. Furthermore, peptide-specific functions of the observed T cells were investigated in more detail. In conclusion, the strong GBM association of IMA950 TUMAPs indicated by over-presentation together with pre-clinical immunogenicity results suggest that this multi-peptide vaccine may benefit the majority of HLA-A*02-positive patients. Clinical development is planned to start within 2010 with several phase I trials investigating the safety and immunogenicity of the vaccine in different patient populations and using various immunomodulatory regimens in order to explore the most promising strategy for further development. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2396.
Neutron star dynamics and gravitational waves
2010-04-01

As several large scale interferometers are beginning to take data at sensitivities where astrophysical sources are predicted, the direct detection of gravitational waves may well be imminent. This would open the gravitational-wave window to our Universe and should lead to a much improved understanding of the most violent processes imaginable; the formation of black holes and neutron stars following core collapse supernovae and the merger of compact objects at the end of binary inspiral. Among the best candidate sources for gravitational waves are the oscillations, but mainly the rotational instabilities of neutron stars which can emit quite strong gravitational wave signals via which one may reveal the details of their structure. Magnetars also are neutron stars with ultra strong magnetic field whose periodic flaring activity is associated with starquakes. They are also a potential source of gravitational waves while even the quasi-periodic oscillations (QPOs) observed in the electromagnetic spectrum can reveal the details of their structure.
1,3-Dialkyl-5-hydroxy-2-thioxoimidazolidin-4-one / 1,3-Dialkyl-5-hydroxy-2-thioxoimidazolidin-4-ones
2010-04-01

The 1,3-dialkyl-5-hydroxy-2-thioxoimidazolidin-4-ones 8 (R = Me, Et, i Pr) were obtained from the corresponding thiourea and glyoxylic acid monohydrate in very good yield. Their reactions with chlorotrimethylsilane in the presence of triethylamine gave the 1,3-dialkyl-5-trimethylsiloxy-2-thioxoimidazolidin- 4-ones 9. NMR and crystal structure data of 1,3-diisopropyl-5-hydroxy-4-thioxoimidazolidin-4-one (8c) have confirmed the acyloin-type structure of the above mentioned compounds.
Abstract 4478: BAY 80-6946, a highly potent and efficacious class I PI3K inhibitor, induces complete tumor regression or tumor stasis in rat xenograft tumor models with PIK3CA mutant or PTEN deletion
2010-04-01

Abstract We report on BAY 80-6946, a highly selective and potent pan class I PI3K inhibitor currently in Phase I clinical trials. The PI3K pathway is aberrantly activated in many tumors either by growth factor receptor tyrosine kinases, or by the genetic mutation and amplification of key pathway components. BAY 80-6946 was evaluated in a panel of human xenograft tumor models. This compound was administered every second (Q2D) day or once weekly using intravenous (i.v.) bolus dosing. BAY 80-6946 was well tolerated with a MTD of 10 mg/kg (Q2D) in athymic rats. In the rat KPL-4 breast tumor model (PIK3CAH1047R and HER2O/E (protein levels)), BAY 80-6946 showed robust and dose-dependent tumor growth inhibition with complete tumor regressions (10/10 CRs) observed at the 3.0 and 6.0 mg/kg doses. The animals remained tumor-free until termination of the study on day 65. BAY 80-6946 also demonstrated complete tumor stasis in the human H460 large cell lung carcinoma and HCT116 colorectal carcinoma models (bearing PIK3CA (E545K and H1047R respectively) along with mutations in KRAS), In U87MG human glioma tumor model (PTEN-deletion) dosed Q2D schedule partial regressions (PRs) were observed. The robust in vivo anti-tumor activities for this class I pan PI3K inhibitor correlated very well with the potent and sustained pharmacodynamic inhibition of p-Akt in tumors, which allowed several i.v. dosing schedules including a once weekly schedule. Thus, BAY 80-6946 given at 6mg/kg, BID once weekly demonstrated similar efficacy as given every other day (Q2D) at 6 mg/kg. Further investigation of pharmacodynamic biomakers revealed that i.v. bolus injection of BAY 80-6946 1 and 6 mg/kg produced a significant dose-dependent reduction in [18F]FDG uptake measured by decrease in SUV in rat H460 tumors supporting the clinical exploration of [18F]FDG imaging to monitor pharmacodynamic drug activity in patients. In conclusion, BAY 80-6946 is a highly efficacious and well tolerated PI3K inhibitor in preclinical rat tumor models expressing HER2, PIK3CA mutant and PTEN-deletion. BAY 80-6946 is currently in phase I clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4478.
To the model of a decagonal Al-Cu-Co
2010-04-01

It is an approach to the model of a decagonal Al-Cu-Co quasicrystal, reproduced from the data of a scanning transmission electron microscopy (STEM) image. The atomic positions, seen on STEM images should be related to an ideal 2-dimensional pentagonal tiling, obtained by the projection from the 4-dimensional A4 root-lattice.
What Can the Pastor Learn from Freud? A Historical Perspective on Psychological and Theological Dimensions of Soul Care
2010-04-01

How should we shape the practice of pastoral care, especially in the context of bioethical counseling? Martin Luther grounded it in a mutual dialogue of brethren. Friedrich Schleiermacher transformed this Protestant understanding according to the modern ideals of freedom and responsibility for oneself. In response to the other basic question of pastoral care: What is the human soul?, Sigmund Freud overcame the Platonic model undergirding Schleiermacher's account. Whoever seeks to care for his own soul and the soul of the other should learn from Freud. One of the most fruitful consequences of such study lies in the formation of a mature religiosity. Another such consequence concerns the pastor's aspiring to an attitude of self-control in counseling. Building one's own competence on the experience and the knowledge of Freud can help one counteract the temptation to transfer one's own (unconscious) wishes onto the conversation partner and conversely to ward off transference from the other onto oneself. On the level of ideals and ultimate principles, however, Christian pastors, unlike Freud, will not see fate and the anonymous forces of Eros and Thanatos, as the ultimate last horizons of human self-understanding. Instead, the good news of sinful man's justification by God transcends even the limits of human existence imposed by fate.
Infection with Cytomegalovirus but not Herpes Simplex Virus induces the accumulation of late differentiated “senescent” T-cells in humans (39.13)
2010-04-01

Abstract Infection with the persistent reactivating human cytomegalovirus (CMV) is associated with an age-associated increasing accumulation of late-differentiated CD8+ T-cells even in asymptomatic healthy carriers. It has been postulated that chronic exposure to any repetitively stimulating antigen (”chronic antigenic stress”) will have similar effects. Here, we have analyzed CMV and HSV infection status in the general population. Detailed analysis of T-cell subsets was performed using 10-colour flow cytometry in 100 individuals aged 40-80 yr. T-cells were characterized according to surface expression of CD45RA, CCR7, CD27 and CD28. Our results demonstrate that T-cell subset distribution was similar in CMV-matched, HSV-seropositive and HSV-seronegative individuals, whereas, in line with our and others previous data, individuals harboring CMV had lower frequencies of naïve T-cells (CD45RA+CCR7+CD27+CD28+) ad a reciprocal accumulation of late-differentiated effector memory (CD45RA-CCR7-CD27-CD28-) and TEMRA (CD45RA+CCR7-CD27-CD28-) subsets. These findings emphasize the apparently unique effect of CMV infection on the human immune system, providing evidence that infection with a different persisting herpesvirus does not show any effects similar to the observed large impact of CMV on the proportions of different T-cell subsets. This work was supported by EU 7FP LifeSpan (LSHG-CT-2007-036894), DFG-SFB685-B4 and DFG-PA 361-11/1
Bifunctional protein for improved stent performance and endothelial regeneration
2010-04-01

Restenosis and thrombosis are undesired effects after stent implantation. Reduced or missing re‐endothelialization of injured coronary arteries shall be abolished by improving stem cell homing at the side of injury to support their differentiation into intact endothelium. We developed a bifunctional protein binding to collagen at the vessel lesion site and to stem/progenitor cells. ELISA studies demonstrated that this bifunctional protein binds to collagen type1 comparably strong as the control protein. Employing stem cell marker overexpressing cells and human CD34 + endothelial progenitor cells on a multi substrate array (MSA) spotted with 14 different extracellular matrix proteins demonstrated the bifunctionality and specificity of the protein. This specificity was substantiated in flow chamber adhesion experiments. Furthermore, we tested colony forming ability and by this endothelial like differentiation of CD34 + ‐cells on fusion protein coated surfaces. In conclusion, this bifunctional protein is a promising construct to support re‐endothelialization and therefore reducing restenosis and thrombosis risk after stent implantation. Supported by the German Ministry of Education and Research (BMBF) # 01GU0727 and 01GU0726.
Functional relations and causality in Fechner and Mach
2010-04-01

In the foundations of Fechner’s psychophysics, the concept of “functional relation” plays a highly relevant role in three different respects: (1) in respect to the principles of measure- ment, (2) in respect to the mind-body problem, and (3) in respect to the concept of a law of nature. In all three cases, it is important to explain the difference between the functional de- pendency of one variable upon another, on the one hand, and the causal relationship between variables on the other. In all three respects, Ernst Mach developed Fechner’s ideas further and tried to extend the lessons of psychophysics learned through the concept of a functional relation to the whole of science. For all three cases, I try to indicate why they are still rele- vant for psychophysics today.