julilili42/papers huggingface dataset:
From Five- to Six-Membered Rings:  3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors
2007-02-27

In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38alphaMAPK IC50 of 1.8 muM. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38alpha- and JNK3-assay, whereas 5 was selective for p38alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compounds, we found a significantly larger distance between the pyridine and the 4-F-phenyl moiety in five-membered core structures relevant for ligand-protein interactions. Molecular modeling studies support the results based on differences in the ATP pockets of p38alpha and JNK3. Because most five-membered core based p38alpha inhibitors show also activity for JNK3, compound 5 is an interesting lead for selective p38alpha inhibitors.
Plio–Quaternary stepwise drying of Asia: Evidence from a 3-Ma pollen record from the Chinese Loess Plateau
2007-02-28

A 3-Ma pollen record was obtained from a continuous red clay- loess-paleosol sequence at Chaona in the central Chinese Loess Plateau (CLP). The record shows a permanent change of a domination of typical Cupressaceae forest vegetation representative of an ecological environment with a relative warm and humid climate during 3.0-2.6 Ma to largely steppe vegetation under dry climate conditions after 2.6 Ma. The later is further manifested itself as steppe to forest or forest-steppe (spruce forest - mostly mesophilous herbs) between 2.6 Ma and 1.5 Ma, forest-steppe (pine-grass) between 1.5 Ma and 0.95 Ma, open forest-steppe (mesophilous and xeromorphic herbs-pine) between 0.95 Ma and 0.5 Ma, and steppe (xeromorphic herbs) after 0.5 Ma, suggesting a process of stepwise aridification in Central Asia at the late Pliocene and the Quaternary. (c) 2007 Elsevier B.V. All rights reserved.
Genetic Variations inPPARDandPPARGC1ADetermine Mitochondrial Function and Change in Aerobic Physical Fitness and Insulin Sensitivity during Lifestyle Intervention
2007-02-28

These data provide evidence that the rs2267668 A/G SNP in PPARD and the Gly482Ser SNP in PPARGC1A have both independent and additive effects on the effectiveness of aerobic exercise training to increase aerobic physical fitness and insulin sensitivity.
Multiple Identities and Work Motivation: The Role of Perceived Compatibility between Nested Organizational Units*
2007-02-28

This study examines the role of perceived compatibility between nested organizational units in identification and work motivation. A survey was conducted in German pharmaceutical stores that had joined a large cooperative network several months before the investigation. Employees judged how compatible the network was with their individual stores on four dimensions (ensuring future, preserving tradition, preserving distinctiveness, and maintaining autonomy). Further, employees indicated their identifications with store and network and their intentions to exert effort on behalf of these units (store motivation and network motivation, respectively). As predicted, perceived compatibility correlated positively with both network identification and network motivation. It also moderated the correlations between store identification and network identification as well as between store motivation and network motivation. Several underlying mechanisms are discussed (e.g. evaluation of store and network, social projection). Overall, perceived compatibility between organizational units appears to be a crucial but under‐researched factor affecting identification and motivation at work.
Preserved Windkessel Function in Patients Following Reduction Aortoplasty of the Ascending Aorta
2007-02-28

Objective: Reduction ascending aortoplasty (RAA) is a controversial procedure. Agreement has not yet been made regarding the indication for surgery and surgical technique. The goal of this study was to examine the long‐term outcome of RAA without external support, and to compare the accuracy of transthoracic echocardiographic with computed tomographic (CT) measurements. Of particular interest was whether the important elastic properties of the aorta, the Windkessel function, is preserved following reduction aortoplasty of the ascending aorta without external wrapping. Methods: Ninety‐eight patients with dilation of the ascending aorta underwent reduction aortoplasty with concomitant cardiac procedures. Fifty‐four patients were available for follow‐up. Measurement of the ascending aortic diameter was performed prior to and directly following surgery, and 37 months postoperatively (range: 10–96 months). Both echocardiography and CT imaging were performed. The elastic properties of the ascending aorta were determined by measuring the distension of the ascending aorta during diastole and systole by means of transthoracic echocardiography. Fifteen patients with graft replacement of the ascending aorta were examined, and the control group contained 11 healthy volunteers. Results: The diameter of the ascending aorta was significantly reduced in all patients who had undergone RAA. The change in diameter between diastole and systole was 3 mm in patients with reduction aortoplasty. Patients with graft replacement had a change of only 0.07 cm. There was no relevant increase (2 mm) in diameter at follow‐up. Echocardiographic and CT measurements of the aortic diameter did not differ. Conclusions: RAA without external wrapping shows good long‐term results in patients with a dilated ascending aorta who underwent concomitant cardiac procedures. Echocardiography is very accurate in measuring the ascending aortic diameter, which makes it a cost‐effective diagnostic tool. Moreover, ascending aortoplasty without external wrapping preserves the important elastic properties, namely the Windkessel function. Follow‐up of the cardiac function and aortic diameter can be performed easily and precisely in the outpatient setting.
The Antagonist Function of Arabidopsis WRKY53 and ESR/ESP in Leaf Senescence Is Modulated by the Jasmonic and Salicylic Acid Equilibrium
2007-03-01

Crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling is well-studied but not during leaf senescence. We found that the senescence-specific WRKY53 transcription factor interacts with the JA-inducible protein EPITHIOSPECIFYING SENESCENCE REGULATOR (ESR/ESP). The expression of these genes is antagonistically regulated in response to JA and SA, respectively, and each negatively influences the other. Leaf senescence is accelerated in ESR knockout plants (ESR-KO) but retarded in ESR overexpressors (ESR-OE), with the reverse true for WRKY53. ESR-OE showed higher resistance than ESR-KO to bacterial and fungal pathogens. However, pathogen resistance was not altered in WRKY53 overexpressors or knockouts (W53-KO), suggesting that ESR has a greater impact on WRKY53 function in senescence than WRKY53 on ESR function in pathogen resistance. ESR inhibits WRKY53 DNA binding in vitro, and their interaction is localized to the nucleus in vivo; however, ESR is exclusively in the cytoplasm in W53-KO cells, indicating that ESR is brought to the nucleus by the interaction. Therefore, ESR has dual functions: as cytoplasmic epithiospecifier and as negative regulator of WRKY53 in the nucleus. These results suggest that WRKY53 and ESR mediate negative crosstalk between pathogen resistance and senescence, which is most likely governed by the JA and SA equilibrium.
Spinal cord injury‐induced immune depression syndrome (SCI‐IDS)
2007-03-01

Abstract Infections are among the leading causes of death in spinal cord‐injured patients, and are associated with hampered wound healing, prolonged hospitalization and impaired neurological recovery. We have analysed fluctuations of immune cell populations in an experimental rat model of spinal cord injury (SCI) by FACS analysis compared with sham‐operated controls to detect the responses specifically induced by SCI. Further, to illustrate the impact of SCI only animals did not receive methylprednisolone in order to exclude confounding iatrogenic factors. Experimental SCI of rats induced a depletion of ED9 + monocytes (&lt; 45%, P &lt; 0.01), CD3 + T‐lymphocytes (&lt; 35%, P &lt; 0.01), CD45 RA + B‐lymphocytes (&lt; 25%, P &lt; 0.01), MHC class II + (&lt; 40%, P &lt; 0.01) and OX‐62 + dendritic cells (&lt; 50%, P = 0.032) within the first week after SCI. HIS 48 + granulocytes remained on levels similar to sham‐operated controls. Our data suggest that experimental SCI induces early onset of an immune suppression that we refer to as SCI‐immune depression syndrome. Iatrogenic application of methylprednisolone in patients suffering may worsen the immune suppression. A deeper understanding of the underlying mechanisms of this novel syndrome might be essential to decrease mortality, costs (time of hospitalization) and to protect the intrinsic neurological recovery potential following SCI.
Platelets and Stromal Cell-Derived Factor-1 in Progenitor Cell Recruitment
2007-03-01

Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that binds to its sole counterreceptor, CXCR4. It is well reported that the SDF-1/CXCR4 signaling pathway is of vital importance to human development and to various pathophysiological phenomena, including hematopoiesis, angiogenesis, atherosclerosis, cancer growth, metastasis, and human immunodeficiency virus infection. SDF-1 promotes mobilization of bone marrow-derived endothelial progenitor cells (EPCs) to the circulation in response to vascular injury. Recently, we found that platelets express and release SDF-1 into the microcirculation upon activation and we observed that platelet-derived SDF-1 is functionally involved in recruitment of EPCs to arterial thrombi in vivo. This review discusses the unique functions of this chemokine and the newly discovered impact of platelet-derived SDF-1 into the recruitment of progenitor cells to vascular injury areas, and its subsequent effects in atherosclerosis, vascular repair, and angiogenesis.
The benefit of using whole‐body, low‐dose, nonenhanced, multidetector computed tomography for follow‐up and therapy response monitoring in patients with multiple myeloma
2007-03-01

Abstract BACKGROUND. The objectives of this study were to assess the status and clinical course of patients with multiple myeloma based on the direct visualization of changes in medullary, extramedullary, and focal osteolytic myeloma involvement by using whole‐body, low‐dose, multidetector computed tomography (WBLD‐MDCT) and to compare those results with an assessment based on conventional hematologic parameters. METHODS. Between June 2002 and December 2005, WBLD‐MDCT scans were obtained from 131 consecutive multiple myeloma patients with or without therapy, resulting in a total of 439 examinations. The number and size of osteolytic lesions and the number, size, and density of focal or diffuse medullary and extramedullary lesions were analyzed. Those results and the results at follow‐up were related to current laboratory tests for myeloma. Validation was achieved by the combined reading of both hematologic and radiologic parameters at follow‐up. RESULTS. Association between both diagnostic modalities was assessed by using European Group for Blood and Marrow Transplantation response criteria, resulting in an agreement of κ = 0.70. Hematologic parameters proved correct in 84% of all examinations, whereas WBLD‐MDCT resulted in correct assessment in 94% of all examinations. Among 91 of 439 examinations that produced discrepant findings (21%), WBLD‐MDCT proved correct in 68 of 91 examinations (75%), as determined at further follow‐up (95% confidence interval, 66–83%; P = .000003; sign test). The combination of WBLD‐MDCT with conventional, laboratory‐based follow‐up resulted in significantly greater diagnostic accuracy compared with laboratory testing alone. CONCLUSIONS. The results from this study indicated that WBLD‐MDCT represents a reliable, imaging‐based method for the direct monitoring of the course of patients with myeloma under specific therapy, and it showed good concordance with established hematologic parameters. It is noteworthy that, in the current investigation, WBLD‐MDCT proved to be even more reliable than conventional, laboratory‐based follow‐up. Cancer 2007. © 2007 American Cancer Society.
Platelets and Endothelial Cells
2007-03-01

The pathogenesis of atherosclerosis, the leading cause of morbidity and mortality in industrial countries, is multifactorial. Atherogenesis, the development of atherosclerotic lesions, is initiated by a mechanical or functional injury of the endothelium. The function of the endothelium is influenced by multiple factors as a consequence of cell-cell interactions. Cell-cell communication between endothelial cells with platelets has only recently begun to receive systematic study. In recent years it has been established that platelet-endothelial interactions are involved at all stages of atherosclerotic disease. This article reviews the interactions between endothelial cells and platelets in the context of their role to initiate and accelerate atherothrombosis, as well as in acute thrombotic occlusion (e.g., at the site of atherosclerotic plaque rupture or subsequent to coronary angioplasty). From a mechanistic standpoint, platelets and endothelial cells communicate on multiple levels. Cross-talk may occur over a distance (paracrine signaling), via transient interactions (so-called give-and-go mechanism), or through receptor-mediated cell-cell adhesion. Platelets may release or transfer substances that influence endothelial cell function, and vice versa. Among many others, adhesion molecules, such as P-selectin (CD62P), are of special interest because of their role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. In addition to dietary, cholesterol and lipid lowering, and other pharmaceutical approaches, antiplatelet therapy plays an important part in the treatment of atherosclerosis and its multifactorial clinical manifestations. Understanding the specific interactions between platelets and the endothelium may lead to the development of novel therapeutic strategies.
Platelet-Leukocyte Interactions in Inflammation and Atherothrombosis
2007-03-01

Inflammatory processes at the vascular wall result in the development of atherosclerosis. Platelet interactions with leukocytes may play a key role in the initiation of inflammation. They trigger autocrine and paracrine activation processes, leading to leukocyte recruitment (in)to the vascular wall. This article highlights the molecular basis and the inflammatory pathways initiated by platelet-leukocyte interactions.
The time-dependent Born-Oppenheimer approximation
2007-03-01

We explain why the conventional argument for deriving the time-dependent Born-Oppenheimer approximation is incomplete and review recent mathematical results, which clarify the situation and at the same time provide a systematic scheme for higher order corrections. We also present a new elementary derivation of the correct second-order time-dependent Born-Oppenheimer approximation and discuss as applications the dynamics near a conical intersection of potential surfaces and reactive scattering.
Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines
2007-03-01

The poor prognosis of patients suffering from malignant glioma requires further efforts. Photodynamic therapy (PDT) might be a therapeutic option to increase surgical radicality. Hypericin (HY) exhibit high phototoxicity to malignant cells and accumulates to a higher extent in glioblastoma cells as compared to neurons. Therefore, the impact of various experimental parameters on cytotoxicity, intracellular accumulation and phototoxicity of HY was quantitatively assessed in the three human glioblastoma cell lines U373 MG, LN229 and T98G. Additionally, intracellular location of HY was studied with fluorescence microscopic techniques. For all three cell lines, no cytotoxicity was found for incubation concentrations up to 5 microM. For short-time incubation (2 h), maximum HY fluorescence was achieved at an incubation concentration of about 5 microM. However, uptake kinetics of HY was dependent on its incubation concentration. Moreover, increase in HY fluorescence was negligible at 4 degrees C, which strongly indicates that the compound is taken up by an energy-dependent process. HY exhibited high phototoxicity (at 595 nm) in all three cell lines with ID50-values ranging from 0.15 J/cm(2) to 0.22 J/cm(2), but sensitivity decreased in the order U373 MG > LN229 > T98G. However, assessment of phototoxicity at different wavelengths revealed that highest cell inactivation was achieved at 600 nm. Fluorescence microscopy showed that HY fluorescence arose predominantly from the perinuclear region and the nuclear membrane. Fluorescence pattern of HY was significantly different from those observed for organelle markers staining lysosomes or mitochondria. Location of HY in the plasma membrane was proven by total internal reflection fluorescence microscopy. Thus, the present study demonstrates that glioblastoma cells can be effectively inactivated by HY-PDT after short-time incubation and exposure to low light doses. These results obtained in cell culture are encouraging and justify further evaluation HY-PDT for the treatment of malignant glioma in animal experiments.
The Evil in Atherosclerosis: Adherent Platelets Induce Foam Cell Formation
2007-03-01

Platelet interaction with circulating progenitor cells plays an important role for repair mechanisms at sites of vascular lesions. Foam cell formation represents a key process in atherosclerotic plaque formation. We revealed that platelets regulate recruitment and differentiation of CD34 (+) progenitor cells into foam cells and endothelial cells. Adhesion studies showed that platelets recruit CD34 (+) progenitor cells via specific adhesion receptors, including P-selection/P-selectin glycoprotein ligand 1, and beta (1) and beta (2) integrins. CD34 (+) progenitor cells were coincubated with human platelets for 1 week. We demonstrated that a substantial number of CD34 (+) cells differentiated into foam cells. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and agonists of peroxisome proliferator-activated receptor-alpha and -gamma (PPAR-alpha and -gamma agonists) reduced this foam cell generation via inhibition of matrix metalloproteinase 9 secretions. Foam cell formation is also induced by low-density lipoproteins (LDLs). It was revealed that platelets take up modified LDL (fluorochrome-conjugated acetylated LDL) that is stored in the dense granules and internalized rapidly into the foam cells. These findings emphasize that the balance between endothelial cell regeneration and platelet-mediated foam cell generation derived from CD34 (+) progenitor cells may play a critical role in atherogenesis and atheroprogression.
Platelet-Induced Differentiation of Endothelial Progenitor Cells
2007-03-01

Endothelial progenitor cells (EPCs) have the potential to home at sites of vascular lesions and to contribute to revascularization. This homing is a highly concerted mechanism, which involves chemotaxis, adhesion, migration, and finally integration of the cells into the target tissue. Only recently has the platelet been identified as a central mediator of EPC homing. Adherent platelets were able to mediate chemotaxis and adhesion of EPCs, a process that involved P-selectin glycoprotein ligand 1 and very late antigen-4 (VLA-4). Recent studies suggest that platelet-derived stromal cell-derived factor-1 is also involved centrally in the recruitment of EPCs. Furthermore, platelets induce progenitor cell migration by platelet-derived growth factor AB. Recent in vivo data confirm the recruitment of EPCs to sites of vascular lesions after vessel denudation by activated platelets and fibrin. Moreover, when coincubated with platelets, EPCs differentiate to mature endothelial cells and have the potential to migrate and colonize a platelet thrombus. The described interaction of EPCs with platelets represents a novel mechanism of vascular remodeling and healing of endothelial lesions.
Who is telling what from where? A functional magnetic resonance imaging study
2007-03-01

The human central-auditory system exhibits distinct lateralization effects (speech, space) and encompasses different processing pathways (where, what, who). Using spatialized pseudoword utterances, attentional modulation of the networks bound to sound source localization ('where'), voice recognition ('who'), and the encoding of phonetic-linguistic information ('what') was evaluated by silent functional magnetic resonance imaging. The 'where'-pathway was found to be restricted to posterior parts of the left superior temporal gyrus, speaker ('auditory face') identification exclusively activated temporal lobe structures, and the representation of the sound structure of the utterances was associated with hemodynamic activation of Broca's area. Speech perception in space, therefore, engages at least three distinct neural networks. Furthermore, the findings indicate that voice recognition may depend upon template matching within auditory association cortex whereas the sequencing of phonetic-linguistic information extends to frontal areas.
The Active Platelet: Translation and Protein Synthesis in an Anucleate Cell
2007-03-01

Platelets are the major cellular component of the hemostatic system that controls vessel and wound repair. However, platelets also have a variety of additional functions in inflammatory responses and host defense. The function and structure of the platelet was assumed to be very simple for a long period of time. With more modern tools of investigation such as cDNA arrays and proteomics, we have discovered a cell that is becoming a more sophisticated libero that functions in the classic mechanisms of white blood cells--inflammation and immunity.
Assessment of Myocardial Viability in a Reperfused Porcine Model
2007-03-01

Good correlation of infarct zones with MRI was achieved for both acute and subacute infarcts. With the use of a bolus/low-flow protocol, image quality was substantially improved by means of a higher tissue contrast.
Regularity of the multi-configuration time-dependent Hartree approximation in quantum molecular dynamics
2007-03-01

\\n \\nWe discuss the multi-configuration\\ntime-dependent Hartree (MCTDH) method for the approximation \\nof the time-dependent Schrödinger equation in quantum molecular dynamics. \\nThis method approximates the high-dimensional nuclear\\nwave function by a linear combination of products of functions depending\\nonly on a single degree of freedom. The \\nequations of motion, obtained via the Dirac-Frenkel \\ntime-dependent variational principle,\\n consist of a coupled system of low-dimensional\\nnonlinear partial differential equations and ordinary differential equations. \\nWe show that, with a smooth and bounded potential, the MCTDH equations \\nare well-posed and retain high-order Sobolev regularity globally in time, that is,\\nas long as the density matrices appearing in the method formulation remain invertible. \\nIn particular, the solutions are regular enough to ensure \\nlocal quasi-optimality of the approximation and to admit an efficient numerical treatment.\\n\\n