julilili42/papers huggingface dataset:
Extracellular Matrix Metalloproteinase Inducer Regulates Matrix Metalloproteinase Activity in Cardiovascular Cells
2006-02-07

Background— Matrix metalloproteinases (MMPs) are thought to promote progression of atherosclerosis and cardiovascular complications such as plaque rupture. It has been suggested that, on tumor cells, the extracellular MMP inducer (EMMPRIN) is involved in MMP synthesis by as yet unknown mechanisms. On cardiovascular cells, regulation of EMMPRIN in vivo or any functional relevance for MMP induction in vitro has not yet been studied. Thus, we studied EMMPRIN expression on monocytes in acute myocardial infarction (MI) and its potential relevance for MMP activation. Methods and Results— In 20 patients with acute MI, surface expression of EMMPRIN was significantly enhanced on monocytes compared with in 20 patients with chronic stable angina. EMMPRIN upregulation was associated with increased expression of the membrane type 1 MMP (MT1-MMP) on monocytes (flow cytometry) as well as MMP-9 activity (gelatin zymography) in the plasma. At 6 months after successful revascularization, EMMPRIN, MT1-MMP, and MMP-9 had normalized. The secretion of MMP-9 by monocytes was induced by monocyte adhesion to immobilized recombinant EMMPRIN or to EMMPRIN-transfected Chinese hamster ovary cells. Moreover, adherent EMMPRIN-transfected monocytic cells stimulated MMP-2 activity of human vascular smooth muscle cells. Gene silencing of EMMPRIN by small-interfering RNA hindered lipopolysaccharide-induced monocyte secretion of MMP-9, indicating a predominant role of EMMPRIN in MMP-9 induction. Conclusions— EMMPRIN and MT1-MMP are upregulated on monocytes in acute MI. During cellular interactions, EMMPRIN stimulates MMP-9 in monocytes and MMP-2 in smooth muscle cells, indicating that EMMPRIN may display a key regulatory role for MMP activity in cardiovascular pathologies.
Canonical Typicality
2006-02-08

It is well known that a system weakly coupled to a heat bath is described by the canonical ensemble when the composite S + B is described by the microcanonical ensemble corresponding to a suitable energy shell. This is true for both classical distributions on the phase space and quantum density matrices. Here we show that a much stronger statement holds for quantum systems. Even if the state of the composite corresponds to a single wave function rather than a mixture, the reduced density matrix of the system is canonical, for the overwhelming majority of wave functions in the subspace corresponding to the energy interval encompassed by the microcanonical ensemble. This clarifies, expands, and justifies remarks made by Schrödinger in 1952.
Neuroimaging Patterns Associated with Motor Control in Traumatic Brain Injury
2006-02-08

Objective. To determine if patients with traumatic brain injury (TBI) and motor deficits show differences in functional activation maps during repetitive hand movements relative to healthy controls. Are there predictors for motor outcome in the functional maps of these patients? Methods. In an exploratory cross-sectional study, functional magnetic resonance imaging (fMRI) was used to study the blood-oxygenation-level-dependent (BOLD) response in cortical motor areas of 34 patients suffering from moderate motor deficits after TBI as they performed unilateral fist-clenching motions. Twelve of these patients with unilateral motor deficits were studied 3 months after TBI and a 2nd time approximately 4 months later. Results. Compared to age-matched, healthy controls performing the same task, TBI patients showed diminished fMRI-signal change in the primary sensorimotor cortex contralateral to the moving hand (cSM1), the contralateral dorsal premotor cortex, and bilaterally in the supplementary motor areas (SMAs). Clinical impairment and the magnitude of the fMRI-signal change in cSM1 and SMA were negatively correlated. Patients with poor and good motor recovery showed comparable motor impairment at baseline. Only patients who evolved to “poor clinical outcome” had decreased fMRI-signal change in the cSM1 during baseline. Conclusions. These observations raise the hypothesis that the magnitude of the fMRI-signal change in the cSM1 region could have prognostic value in the evaluation of patients with TBI.
Comparative proteome analysis of Staphylococcus aureus biofilm and planktonic cells and correlation with transcriptome profiling
2006-02-09

Abstract Pathogenic staphylococci can form biofilms in which they show a higher resistance to antibiotics and the immune defense system than their planktonic counterparts, which suggests that the cells in a biofilm have an altered metabolic activity. Here, 2‐D PAGE was used to identify secreted, cell wall‐associated and cytoplasmic proteins expressed in Staphylococcus aureus after 8 and 48 h of growth. The proteins were separated at pH ranges of 4–7 or 6–11. The protein patterns revealed significant differences in 427 protein spots; from these, 258 non‐redundant proteins were identified using ESI‐MS/MS. Biofilm cells expressed higher levels of proteins associated with cell attachment and peptidoglycan synthesis, and in particular fibrinogen‐binding proteins. Enzymes involved in pyruvate and formate metabolism were upregulated. Furthermore, biofilm cells expressed more staphylococcal accessory regulator A protein (SarA), which corroborates the positive effect of SarA on the expression of the intercellular adhesion operon ica and biofilm growth. In contrast, proteins, such as proteases and particularly immunodominant antigen A (IsaA) and staphylococcal secretory antigen (SsaA), were found in lower amounts. The RNA expression profiling largely supports the proteomic data. The results were mapped onto KEGG pathways.
Lipolanthionine Peptides Act as Inhibitors of TLR2-Mediated IL-8 Secretion. Synthesis and Structure−Activity Relationships
2006-02-09

Lipoproteins from gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers. For this reason, these compounds constitute highly active adjuvants for vaccines either admixed or covalently linked. The lanthionine scaffold has structural similarity with the S-(2,3-dihydroxypropyl)cysteine core structure of the lipopeptides. Therefore, lanthionine-based lipopeptide amides were synthesized and probed for activity as potential TLR2 agonists or antagonists. A collection of analytically defined lipolanthionine peptide amides exhibited an inhibitory effect of the TLR2-mediated IL-8 secretion when applied in high molar excess to the agonistic synthetic lipopeptide Pam3Cys-Ser-(Lys)4-OH. Structure-activity relationships revealed the influence of the chirality of the two alpha-carbon atoms, the chain lengths of the attached fatty acids and fatty amines, and the oxidation level of the sulfur atom on the inhibitory activity of the lipolanthionine peptide amides.
Highlighting the role of the chlorine substituents in the glycopeptide antibiotic balhimycin for chiral recognition in capillary electrophoresis
2006-02-09

Abstract The vancomycin‐type glycopeptide antibiotic balhimycin ( I ) and its dehaloanalogue dechlorobalhimycin ( III ), which is characterized by the total substitution of the two chlorine atoms of I by hydrogen, were employed as chiral selectors for the enantioresolution of 11 racemic dansyl amino acids and six 2‐arylpropionic acid nonsteroidal anti‐inflammatory racemic drugs by CE. The observed enantioresolution capability of I for all test analytes is clearly higher than that observed for III . This result suggests that chlorine substituents of I played a major role in the enantioresolution of these test analytes. A dimerization‐based mechanism is proposed in order to explain this phenomenon. The two chlorine substituents of each monomer, which mutually penetrate into the cavity of the adjacent molecule of the dimer, are assumed to promote dimerization and as a consequence also enantioresolution.
Cognitive function in multiple system atrophy of the cerebellar type
2006-02-10

Abstract Dementia represents an exclusion criterion for the diagnosis of multiple system atrophy (MSA), but there have been reports of fronto‐executive dysfunction in patients with MSA of the striatonigral type (MSA‐P). To study the cognitive profile of MSA, 20 patients with MSA of the cerebellar type (MSA‐C) were subjected to an extensive neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory, as well as executive function. There was evidence for impaired verbal memory and verbal fluency. Test performance was not related to the severity of motor disability. Regarding the similar cognitive syndrome of MSA‐P, the otherwise subclinical problems in MSA‐C result from subcortical rather than from cerebellar dysfunction. © 2006 Movement Disorder Society
Efficient visual homing based on Fourier transformed panoramic images
2006-02-10

We present a fast and efficient homing algorithm based on Fourier transformed panoramic images. By continuously comparing Fourier coefficients calculated from the current view with coefficients representing the goal location, a mobile robot is able to find its way back to known locations. No prior knowledge about the orientation with respect to the goal location is required, since the Fourier phase is used for a fast sub-pixel orientation estimation. We present homing runs performed by an autonomous mobile robot in an office environment. In a more comprehensive investigation the algorithm is tested on an image data base recorded by a small mobile robot in a toy house arena. Catchment areas for the proposed algorithm are calculated and compared to results of a homing scheme described in [M. Franz, B. Schölkopf, H. Mallot, H. Bülthoff, Where did I take that snapshot? Scene based homing by image matching, Biological Cybernetics 79 (1998) 191-202] and a simple homing strategy using neighbouring views. The results show that a small number of coefficients is sufficient to achieve a good homing performance. Also, a coarse-to-fine homing strategy is proposed in order to achieve both a large catchment area and a high homing accuracy: the number of Fourier coefficients used is increased during the homing run.
Application of Transcranial Sonography in Extrapyramidal Disorders: Updated Recommendations
2006-02-10

Transcranial sonography (TCS) has been proven to be a valuable tool in the diagnosis and differential diagnosis of extrapyramidal disorders, supplementing clinical and pathophysiological information that may be obtained by other neuroimaging techniques. Growing interest and increased application of TCS in extrapyramidal disorders require adherence to standardised principles concerning examination procedure and parameter settings of the ultrasound machine in order to ensure comparable results. This article provides an overview of these principles and typical findings in distinct extrapyramidal disorders.
Chemoenzymatic Synthesis of the C10−C23 Segment of Dictyostatin
2006-02-11

[reaction: see text] Employing enzymatic desymmetrization and resolution, respectively, the two aldehydes 8 and 20 were prepared. The precursor to aldehyde 8, meso-2,4-dimethylglutaric anhydride 3, could be obtained by base treatment of the diastereomeric mixture. Aldehyde 8 was extended to alkyne 10 by a Marshall reaction introducing four carbon atoms. Lithiation of the derived iodide 15 and trapping of the anion with amide 22 gave ketone 23. This compound led to the C10-C23 fragment 27 of dictyostatin.
Interaction of Acid-sensing Ion Channel (ASIC) 1 with the Tarantula Toxin Psalmotoxin 1 is State Dependent
2006-02-13

Acid-sensing ion channels (ASICs) are Na+ channels gated by extracellular H+. Six ASIC subunits that are expressed in neurons have been characterized. The tarantula toxin psalmotoxin 1 has been reported to potently and specifically inhibit homomeric ASIC1a and has been useful to characterize ASICs in neurons. Recently we have shown that psalmotoxin 1 inhibits ASIC1a by increasing its apparent affinity for H+. However, the mechanism by which PcTx1 increases the apparent H+ affinity remained unclear. Here we show that PcTx1 also interacts with ASIC1b, a splice variant of ASIC1a. However, PcTx1 does not inhibit ASIC1b but promotes its opening; under slightly acidic conditions, PcTx1 behaves like an agonist for ASIC1b. Our results are most easily explained by binding of PcTx1 with different affinities to different states (closed, open, and desensitized) of the channel. For ASIC1b, PcTx1 binds most tightly to the open state, promoting opening, whereas for ASIC1a, it binds most tightly to the open and the desensitized state, promoting desensitization.
Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells
2006-02-14

Abstract Proteasome inhibitors possess potent antitumor activity against a broad spectrum of human malignancies. However, the effects of these compounds on the immune system still have to be clearly determined. In the present study, we have investigated the effects of proteasome inhibitors on dendritic cells (DC), antigen‐presenting cells playing a key role in the initiation of immune responses. Exposure to the proteasome inhibitors bortezomib, MG132 or epoxomicin was found to promote apoptosis of human monocyte‐derived DC and to reduce the yield of viable DC when given to monocytes early during differentiation to DC. DC apoptosis via proteasome inhibition was accompanied by mitochondria disruption and subsequent activation of the caspase cascade. Up‐regulation and intracellular redistribution of Bcl‐2‐associated X protein (Bax), a pro‐apoptotic Bcl‐2 family protein, were observed in DC treated with these compounds and represent a suitable mechanism leading to activation of the intrinsic apoptotic pathway. Finally, active protein synthesis was found to represent an upstream prerequisite for DC apoptosis induced by proteasome inhibitors, since the translation inhibitor cycloheximide blocked all of the steps of the observed apoptotic response. In conclusion, induction of apoptosis in DC may represent a novel mechanism by which proteasome inhibitors affect the immune response at the antigen‐presenting cell level.
Longitudinal Studies of Clonally Expanded CD8 T Cells Reveal a Repertoire Shrinkage Predicting Mortality and an Increased Number of Dysfunctional Cytomegalovirus-Specific T Cells in the Very Elderly
2006-02-15

Abstract The age-associated decrease in functionality of the human immune system is thought to have a negative impact on the capacity to provide protection against infection, in turn leading to increased incidence of mortality. In a previous longitudinal study of octogenarians, we identified an immune risk phenotype (IRP) in the very elderly defined by an inverted CD4/CD8 ratio, which was associated with increased mortality and persistent CMV infection. In this study, we analyzed the CD8 clonal composition of nonagenarians and middle-aged individuals. An increased number of CD8 T cell clones was observed in the nonagenarians, and was associated with CMV-seropositivity. Surprisingly, CMV-seropositive nonagenarians with the IRP had a significantly lower number of clones compared with non-IRP individuals. The decrease in clone numbers in IRP individuals was associated with shorter survival time. MHC/peptide multimer staining indicated that the frequency of CMV-specific T cells was higher in nonagenarians than in the middle-aged, but the ratio of functionally intact cells was significantly lower. The lowest ratio of functional CMV-specific T cells was found in an IRP individual. A thorough longitudinal analysis of the CMV-specific T cells in nonagenarians showed a stable pattern with respect to frequency, phenotype, and clonal composition. We hypothesize that the number of different CD8 T cell clonal expansions increases as the individual ages, possibly, as a compensatory mechanism to control latent infections, e.g., CMV, but eventually a point is reached where clonal exhaustion leads to shrinkage of the CD8 clonal repertoire, associated with decreased survival.
Brain–computer interfaces for communication and control
2006-02-16

As a communication and control system, a brain-computer interface (BCI) establishes a real-time interaction between the user and the outside world. Human BCI experience to date has been confined almost entirely to electroencephalographic (EEG) studies and short-term electrocorticographic activity (EcoG) studies. A BCI records brain signals and processes them to produce device commands. This signal processing has two stages. The first stage is feature extraction, the calculation of the values of specific features of the signals. The second stage is a translation algorithm that translates these features into device commands. The eventual extent and impact of BCI applications depend on the speed and precision of the control that can be achieved and on the reliability and convenience of their use. Simple BCI applications appear to have a secure future in their potential to make a difference in the lives of extremely disabled people.
The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling
2006-02-17

The stress-responsive serum- and glucocorticoid-inducible kinase Sgk-1 is involved in osmoregulation and cell survival and may contribute to fibrosis and hypertension. However, the function of Sgk-1 in vascular remodeling and thrombosis, 2 major determinants of pulmonary hypertension (PH), has not been elucidated. We investigated the role of Sgk-1 in thrombin signaling and tissue factor (TF) expression and activity in pulmonary artery smooth muscle cells (PASMC). Thrombin increased Sgk-1 activity and mRNA and protein expression. H 2 O 2 similarly induced Sgk-1 expression. Antioxidants, dominant-negative Rac, and depletion of the NADPH oxidase subunit p22phox diminished thrombin-induced Sgk-1 expression. Inhibition of p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and phosphoinositide-dependent kinase-1 prevented thrombin-induced Sgk-1 expression. Thrombin or Sgk-1 overexpression enhanced TF expression and procoagulant activity, whereas TF upregulation by thrombin was diminished by kinase-deficient Sgk-1 and was not detectable in fibroblasts from mice deficient in sgk-1 (sgk1 −/− ). Similarly, dexamethasone treatment failed to induce TF expression and activity in lung tissue from sgk1 −/− mice. Transcriptional induction of TF by Sgk-1 was mediated through nuclear factor κB. Finally, Sgk-1 and TF proteins were detected in the media of remodeled pulmonary vessels associated with PH. These data show that thrombin potently induces Sgk-1 involving NADPH oxidases, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and phosphoinositide-dependent kinase-1, and that activation of nuclear factor κB by Sgk-1 mediates TF expression and activity by thrombin. Because enhanced procoagulant activity can promote pulmonary vascular remodeling, and Sgk-1 and TF were present in the media of remodeled pulmonary vessels, this pathway may play a critical role in vascular remodeling in PH.
Let the captives speak for themselves! More dialogue between religious education in England and Germany
2006-02-17

This article offers a German response to John Hull's recent article on ‘religious education in Germany and England’ (in BJRE, volume 27, issue 1). The author claims that recent developments have brought religious education in both countries much closer together than in the past and that the differences between the respective systems should be understood contextually. In his view, more complex approaches to comparative research in religious education are needed. Agreement should be sought in terms of criteria for quality religious education rather than in terms of a unitary model because religious education in different countries needs a pluralism of different models.
Multifocal ERG Changes in Patients with Ocular Behçet’s Disease During Therapy with Interferon alpha 2a
2006-02-18

Previously, we have shown the efficacy of IFNα2a in BD patients with posterior uveitis or panuveitis achieved by marked improvement of visual acuity due to reduction of inflammatory retinal changes1. Now we could demonstrate this benefiting therapeutic effect by measurement of the multifocal ERG. Most of the affected eyes disclosed amplitude changes in the mfERG. These areas correspond to the macular- and the nearer perimacular region; therefore the amplitude alterations might be caused by inflammatory macular changes, esp. macular edema3–5. In patients with posterior uveitis or panuveitis due to BD treated with IFNα2a, the mfERG clearly reflects the clinical course and is an objective follow-up of macular dysfunction in recurrent uveitis. Reduced ERG amplitudes were observed in the macular region in all eyes with macular edema or secondary inflammatory changes with remarkable improvement in patients with acute uveitis. Implicit time changes were seen in progressed cases of chronic or recurrent macular edema. Thus, only in chronic eye disease with advanced stages no improvement of both amplitude and implicit time was detectable. The mfERG seems to have no direct correlation to visual acuity but indeed to duration and severity of ocular disease. In conclusion, the mfERG reflects very well the extent of damage to the central retina due to ocular inflammation in BD patients with otherwise (visual acuity / ophthalmoscopy) absent pathological values.
Interferon alpha 2a in IRPB-derived Peptide-induced EAU — Part I
2006-02-18

Clinically, the IFN-α treated animals exhibited minimal disease, compared to the control group. These findings have been histologically confirmed. Using a variety of monoclonal antibodies, we were not able to demonstrate any differences for panCD44 expression. The similar expression pattern of panCD44 in the retina between control and IFN-α treated mice indicates that this expression may be not influenced by the applied IFN-α dosage. The panCD44 homing receptor may be important for the regulation of EAU induction by CD45+ and CD3+ T-cells. Differences have been observed for CD45+ infiltration between control and IFN-α treated animals. This may be an important hint to characterize their function by markers others than CD8 and CD4 specific antibodies, especially for their T-cell receptor (TCR) expression (α/β versus γ/δ). To identify further differences between IFN-α treated and control mice our analyses will be extended to antigen presenting cells (APC), especially to dendritic cells (DC) capable to regulate the Th1/Th2 balance. Additionally, these analyses will be extended to cell adhesion molecules and/or homing receptor expression kinetics regulated by chemo-and cytokines. EAU induction experiments are presently performed with an increased IFN-α dosage correlating with the surface (m2) of human beings to clarify our results.
Behçet’s Disease: Visual Acuity after 5 Years in Patients with Alpha-Interferon Treatment
2006-02-18

ConclusionCompared to conventional immunosuppressants, IFN-α2a seems to be much more effective to prevent a loss or decrease of visual acuity over a long period of time in patients with severe ocular BD.As 15 eyes is only a small case series, further evaluation is needed. We expect that in approximately 12 months 30 eyes will have reached the 5-year follow-up mark, so more data will soon then be available.
Influence of Interferon-alpha on Lymphocyte Subpopulations in Behçet’s Disease
2006-02-18

In Behcet’s disease (BD)‚ several abnormalities of lymphocyte subpopulations such as an elevation of NK and T-cells have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon (response rate 92%) which is counterintuitive because is immunostimulatory and can sometimes even induce autoimmune diseases such as SLE or RA. The aim of this study was to elucidate the immunomodulatory effects that might exert in BD.