julilili42/papers huggingface dataset:
Aerobically Derived Lactate Stimulates Revascularization and Tissue Repair via Redox Mechanisms
2007-06-14

Hypoxia serves as a physiologic cue to drive an angiogenic response via HIF-dependent mechanisms. Interestingly, minor elevation of lactate levels in the tissue produces the same effect under aerobic conditions. Aerobic glycolysis contributes to lactate accumulation in the presence of oxygen, especially under inflammatory conditions. We previously postulated that aerobic lactate accumulation, already known to stimulate collagen deposition, will also stimulate angiogenesis. If substantiated, this concept would advance understanding of wound healing and aerobic angiogenesis because lactate accumulation has many aerobic sources. In this study, Matrigel plugs containing a powdered, hydrolyzable lactate polymer were implanted into the subcutaneous space of mice. Lactate monomer concentrations in the implant were consistent with wound levels for more than 11 days. They induced little inflammation but considerable VEGF production and were highly angiogenic, as opposed to controls. Arterial hypoxia abrogated angiogenesis. Furthermore, inhibition of lactate dehydrogenase by using oxamate also prevented the angiogenic effects of lactate. Lactate monomer, at concentrations found in cutaneous wounds, stabilized HIF-1alpha and increased VEGF levels in aerobically cultured human endothelial cells. Accumulated lactate, therefore, appears to convey the impression of "metabolic need" for vascularization, even in well-oxygenated and pH-neutral conditions. Lactate and oxygen together stimulate angiogenesis and matrix deposition.
Enhanced susceptibility to suicidal death of erythrocytes from transgenic mice overexpressing erythropoietin
2007-06-14

Eryptosis, a suicidal death of mature erythrocytes, is characterized by decrease of cell volume, cell membrane blebbing, and breakdown of cell membrane asymmetry with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increased cytosolic Ca 2+ activity, which could result from activation of Ca 2+ -permeable cation channels. Ca 2+ triggers phosphatidylserine exposure and activates Ca 2+ -sensitive K + channels, leading to cellular K + loss and cell shrinkage. The cation channels and thus eryptosis are stimulated by Cl − removal and inhibited by erythropoietin. The present experiments explored eryptosis in transgenic mice overexpressing erythropoietin (tg6). Erythrocytes were drawn from tg6 mice and their wild-type littermates (WT). Phosphatidylserine exposure was estimated from annexin binding and cell volume from forward scatter in fluorescence-activated cell sorting (FACS) analysis. The percentage of annexin binding was significantly larger and forward scatter significantly smaller in tg6 than in WT erythrocytes. Transgenic erythrocytes were significantly more resistant to osmotic lysis than WT erythrocytes. Cl − removal and exposure to the Ca 2+ ionophore ionomycin (1 μM) increased annexin binding and decreased forward scatter, effects larger in tg6 than in WT erythrocytes. The K + ionophore valinomycin (10 nM) triggered eryptosis in both tg6 and WT erythrocytes and abrogated differences between genotypes. An increase of extracellular K + concentration to 125 mM blunted the difference between tg6 and WT erythrocytes. Fluo-3 fluorescence reflecting cytosolic Ca 2+ activity was larger in tg6 than in WT erythrocytes. In conclusion, circulating erythrocytes from tg6 mice are sensitized to triggers of eryptosis but more resistant to osmotic lysis, properties at least partially due to enhanced Ca 2+ entry and increased K + channel activity.
Conformational distribution of a ferroelectric liquid crystal revealed using fingerprint vibrational spectroscopy and the density functional theory
2007-06-14

The authors have investigated the conformational structure of the ferroelectric liquid crystal compound 4-3-methyl-2-chloropentanoyloxy-4′′-hexyloxy-biphenyl also known under the abbreviations 3M2CPHOB and C6 using vibrational (IR and Raman) spectroscopy. The measured spectra exhibit two bands corresponding to the CO stretching vibration that are separated by 20cm−1. In contrast, the molecular structure comprises only one such group. They assigned the two bands to different conformers that coexist in a temperature range between 25 and 65°C covering the entire mesophase of this material. This assignment is strongly confirmed by calculated vibrational spectra based on the density functional theory.
Multivariate distribution of returns in financial time series
2007-06-14

Multivariate probability density functions of returns are constructed in order to model the empirical behavior of returns in a financial time series. They describe the well-established deviations from the Gaussian random walk, such as an approximate
Zr50Sc12O43N50 and Zr3Sc4N8 —Synthesis, Neutron Powder Diffraction and Raman Spectroscopy.
2007-06-14

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Two Tungsten Nitride Chlorides: W2NCl8 and W2NCl9.
2007-06-14

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Lifestyle intervention in individuals with normal versus impaired glucose tolerance
2007-06-15

Abstract Background Lifestyle intervention is effective in the prevention of type 2 diabetes in individuals with impaired glucose tolerance (IGT). It is currently unknown whether it has beneficial effects on metabolism to a similar extent, in individuals with normal glucose tolerance (NGT) compared to individuals with IGT. Materials and methods Data from 181 subjects (133 with NGT and at risk for type 2 diabetes and 48 with IGT) who participated in the Tuebingen Lifestyle Intervention Program with increase in physical activity and decrease in caloric intake were included into this study. Body fat distribution was quantified by whole‐body magnetic resonance (MR) tomography and liver fat and intramyocellular fat by 1 H‐MR spectroscopy. Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT). Results After 9 ± 2 months of follow‐up, the diagnosis of IGT was reversed in 24 out of 48 individuals. Only 14 out of 133 participants with NGT developed IGT. Body weight decreased in both groups by 3% (both P &lt; 0·0001). Two‐hour glucose concentrations during an OGTT decreased in individuals with IGT (–14%, P &lt; 0·0001) but not with NGT (+2%, P = 0·66). Insulin sensitivity increased both in individuals with IGT (+9%, P = 0·04) and NGT (+17%, P &lt; 0·0001). Visceral fat (–8%, P = 0·006), liver fat (–28%, P &lt; 0·0001) and intramyocellular fat (–15%, P = 0·006) decreased in participants with IGT. In participants with NGT these changes were significant for visceral fat (–16%, P &lt; 0·0001) and liver fat (–35%, P &lt; 0·0001). Conclusions Moderate weight loss under a lifestyle intervention with reduction in total, visceral and ectopic fat and increase in insulin sensitivity improves glucose tolerance in individuals with IGT but not with NGT. In individuals with NGT, the beneficial effects of a lifestyle intervention on fat distribution and insulin sensitivity possibly prevent future deterioration in glucose tolerance.
Migration-assisted nonlinear quenching in random media
2007-06-15

A simple and highly accurate model is presented for the decay of the excited state density of randomly distributed luminescent centers (e.g., rare-earth ions or fluorescent dyes) affected by migration-assisted nonlinear quenching (e.g., upconversion or singlet-singlet annihilation). The model relates quenching efficiency, interpreted in terms of the time-dependent quenching coefficient, to parameters of underlying Förster energy transfer phenomena and to center concentration. The accuracy of the model is verified by comparison with Monte Carlo simulations. The model sets up a rigorous basis for the characterization of nonlinear quenching in Er-doped glasses and disordered organic optoelectronic materials.
Alteration of NF-κB activity leads to mitochondrial apoptosis after infection with pathological prion protein
2007-06-16

Nuclear factor kappa B (NF-kappaB) is a key regulator of the immune response, but in almost the same manner it is involved in induction of inflammation, proliferation and regulation of apoptosis. In the central nervous system activated NF-kappaB plays a neuroprotective role. While in some neurodegenerative disorders the role of NF-kappaB is well characterized, there is poor knowledge on the role of NF-kappaB in prion disease. We found binding but no transcriptional activity of the transcription factor in vitro. Characterizing the mechanism of cell death after infection with pathological prion protein increased caspase-9 and caspase-3 activity was detected and the lack of NF-kappaB activity resulted in the inability to activate target genes that usually play an important role in neuroprotection. Additionally, we investigated the role of NF-kappaB after prion infection of Nfkb1(-/-), Nfkb2(-/-) and Bcl3(-/-) mice and central nervous system-specific p65-deleted mice revealing an accelerated prion disease in NF-kappaB2- and Bcl-3-deficient mice, which is in line with a reduced neuroprotective activity in prion infection. Based on our findings, we propose a model whereby the alteration of NF-kappaB activity at the early stages of infection with pathological prion protein leads to neuronal cell death mediated by mitochondrial apoptosis.
Overexpression of Acid Sphingomyelinase Sensitizes Glioma Cells to Chemotherapy
2007-06-18

Ceramide has been shown by many studies to induce apoptosis. Therefore, upregulation of ceramide is discussed as a novel approach for tumor treatment. However, it is unknown whether overexpression of acid sphingomyelinase releasing ceramide from sphingomyelin sensitizes cells to chemotherapy and, thus, serves as a potential target to amplify chemotherapy. Here, the authors demonstrate that transfection of human or murine glioma cells with acid sphingomyelinase results in a marked sensitization of glioma cells to gemcitabine and doxorubicin, respectively. Transfected cells responded to chemotherapy with an increased activation of acid sphingomyelinase, elevated ceramide levels, and approximately fourfold higher rates of cell death than control transfected cells. Neutralization of reactive oxygen species prevented these events. The data indicate a significant sensitization of glioma cells to chemotherapy treatment by expression of acid sphingomyelinase and further suggest an activation of acid sphingomyelinase by gemcitabine or doxorubicin, respectively, via reactive oxygen species.
Comparative analysis of structured RNAs in S. cerevisiaeindicates a multitude of different functions
2007-06-18

Abstract Background Non-coding RNAs (ncRNAs) are an emerging focus for both computational analysis and experimental research, resulting in a growing number of novel, non-protein coding transcripts with often unknown functions. Whole genome screens in higher eukaryotes, for example, provided evidence for a surprisingly large number of ncRNAs. To supplement these searches, we performed a computational analysis of seven yeast species and searched for new ncRNAs and RNA motifs. Results A comparative analysis of the genomes of seven yeast species yielded roughly 2800 genomic loci that showed the hallmarks of evolutionary conserved RNA secondary structures. A total of 74% of these regions overlapped with annotated non-coding or coding genes in yeast. Coding sequences that carry predicted structured RNA elements belong to a limited number of groups with common functions, suggesting that these RNA elements are involved in post-transcriptional regulation and/or cellular localization. About 700 conserved RNA structures were found outside annotated coding sequences and known ncRNA genes. Many of these predicted elements overlapped with UTR regions of particular classes of protein coding genes. In addition, a number of RNA elements overlapped with previously characterized antisense transcripts. Transcription of about 120 predicted elements located in promoter regions and other, previously un-annotated, intergenic regions was supported by tiling array experiments, ESTs, or SAGE data. Conclusion Our computational predictions strongly suggest that yeasts harbor a substantial pool of several hundred novel ncRNAs. In addition, we describe a large number of RNA structures in coding sequences and also within antisense transcripts that were previously characterized using tiling arrays.
An experimental test of the maintenance and vulnerability hypothesis of depression in consideration of the cognitive hierarchy
2007-06-18

According to Beck's cognitive model of depression the activation of dysfunctional beliefs triggers negative automatic thoughts, which can be interpreted as the proximal "cause" for emotional, somatic, and motivational symptoms of depression. This top-down processes of beliefs causing thoughts and furthermore of thoughts causing symptoms can be called "cognitive hierarchy." Besides these processes there are bottom-up influences as well with dysfunctional beliefs being activated by external and internal events. A differentiation between top-down processes and bottom-up influences can be drawn with the first being seen as causing thoughts and emotions while the latter only activate existing beliefs. To test Beck's maintenance and the vulnerability hypothesis considering the cognitive hierarchy we suggest an experimental paradigm to experimentally manipulate beliefs, thoughts, and emotions separately and independent from each other. To test both hypotheses in an experimental paradigm depressed and nondepressed subjects are asked to concentrate on new beliefs, thoughts, or emotions during the imagination of personally stressful life events in two studies. Based on the top-down processes it was posited that concentration on new beliefs should lead to changes on all three levels of experience. Adding a new thought should cause changes on the levels of thoughts and emotions while new emotions should only change the level of emotions. The results confirm our hypotheses concerning beliefs and thoughts, but adding emotions changes the levels of thoughts as well as emotions. The results support the central role of beliefs in the development and maintenance of depressive symptoms.
Microstructures by Selective Desorption of Self‐Assembled Monolayer from Polycrystalline Gold Electrodes
2007-06-18

Abstract Potential‐controlled partial reductive desorption of a self‐assembled monolayer of mercaptopropionic acid (MPA) formed on polycrystalline gold electrodes is used to expose subdomains of bare gold to the electrolyte solution. Two sets of cathodic waves are observed in the reduction scan with MPA self‐assembled on a polycrystalline gold electrode. The origin of the two waves is ambiguous but there are indications that the waves are correlated with reductive desorption from the (111) and then simultaneously (100) and (110) index faces of a polycrystalline gold electrode. Consecutive reduction scans with reversing the potential direction after the first peak (but before the onset of the second wave) results in disappearance of the first wave. The exposed domains are then blocked by an assembling process of longer chain alkanethiols to create a mixed self‐assembled monolayer on polycrystalline gold electrodes. Desorption of the remaining MPA creates a partially blocked electrode and the blocking behavior towards hexacyanoferrate(III) is analyzed using the theory of partially blocked electrodes and indicates an array of interacting centers. The approach of partial reductive desorption may be exploited for use in biosensing applications where the exposed gold domains could be used for anchoring of DNA probes.
Imaging of thermal domains in ultrathin NbN films for hot electron bolometers
2007-06-18

The authors present low-temperature scanning electron microscopy (LTSEM) investigations of superconducting microbridges made from ultrathin NbN films as used for hot electron bolometers. LTSEM probes the thermal structure within the microbridges under various dc bias conditions, either via electron-beam-induced generation of an unstable hot spot or via the beam-induced growth of a stable hot spot. Such measurements reveal inhomogeneities on a micron scale, which may be due to spatial variations in the NbN film or film-interface properties. Comparison with model calculations for the stable hot spot regime confirms the basic features of common hot spot models.
Endosomal signaling of plant steroid receptor kinase BRI1
2007-06-19

The LRR receptor serine/threonine kinases are a major eukaryotic receptor family, for which the central regulatory mechanism of endosomal trafficking remains largely unadressed. We show that the steroid receptor BRI1 localizes to both plasma membrane and early endosomal compartments, even when observed at low, endogenous expression levels, and that its localization and turnover are independent of ligand. However, increasing endosomal localization of BRI1 enhances activation of the pathway and genomic responses. Our data indicate distinct signaling and trafficking mechanisms within this receptor class and show that the use of endosomes as signaling compartments is an unexpectedly broad phenomenon in eukaryotes.
Chemoenzymatic Synthesis of Prenylated Indole Derivatives by Using a 4‐Dimethylallyltryptophan Synthase from Aspergillus fumigatus
2007-06-19

Abstract A 4‐dimethylallyltryptophan synthase, FgaPT2, has been identified in the genome of Aspergillus fumigatus . In a previous study, FgaPT2 was overexpressed in Saccharomyces cerevisiae and characterized biochemically. A higher protein yield (up to 100‐fold higher than that for S. cerevisiae) has now been achieved by overexpression in E. coli; this has permitted investigation into substrate specificity with alternative substances. FgaPT2 accepted 17 of 37 commercially available indole derivatives as substrates. Tryptophan derivatives that carry methyl groups at the indole ring showed a different acceptance from those with methyl groups on the side chain. 5‐Hydroxytryptophan was well accepted by FgaPT2, while the halogenated derivatives were not accepted. Decarboxylation, deamination, or oxidative deamination of tryptophan, as well as replacement of the NH 2 group by OH, or of the COOH group by CH 2 COOH or CONHOH resulted in decreased but still significant enzymatic activity. None of the tested tryptophan‐containing dipeptides was accepted by FgaPT2. Structural elucidation of isolated enzymatic products by NMR and MS analyses proved unequivocally that the prenylation was regioselective at position C4 of the indole ring in the presence of dimethylallyl diphosphate. Determination of the kinetic parameters revealed that L ‐tryptophan was accepted as the best substrate by the enzyme, followed by 5‐,6‐,7‐methyltryptophan and L ‐abrine. The enzymatic rate constant ( k cat K m −1 ) of nine selected substrates were found to be about 1.0 to 6.5 % of that for L ‐tryptophan. Overnight incubation with eight substances showed that the conversion ratio to their prenylated derivatives was in the range 32.5 to 99.7 %. This provides evidence that 4‐dimethylallylated indole derivatives can be produced by chemoenzymatic synthesis with FgaPT2.
Radiologic Spectrum of Extramedullary Relapse of Myelogenous Leukemia in Adults
2007-06-19

Allogeneic stem cell transplantation now represents the treatment of choice for leukemia and for patients with leukemia relapse. Therefore, the rate of chloroma is likely to increase. Because clinical and laboratory data are frequently not indicative, radiologic diagnosis of chloroma will become more important.
Collapsed But Not Folded: Looking with Advanced Optical Spectroscopy at Protein Folding
2007-06-19

The intermediate folding step: The highlight discusses a recent study by Hoffman et al. on the collapsed but still unfolded state of a small protein under close to native conditions. This collapsed unfolded state (see picture) is an important intermediate between the completely denatured, unfolded and the completely folded, native protein structure and is thought to be of paramount importance for the final folding.
Cavity-enhanced superradiant Rayleigh scattering with ultracold and Bose-Einstein condensed atoms
2007-06-20

We report on the observation of collective atomic recoil lasing and superradiant Rayleigh scattering with ultracold and Bose-Einstein condensed atoms in an optical ring cavity. Both phenomena are based on instabilities evoked by the collective interaction of light with cold atomic gases. This publication clarifies the link between the two effects. The observation of superradiant behavior with thermal clouds as hot as several tens of proves that the phenomena are driven by the cooperative dynamics of the atoms, which is strongly enhanced by the presence of the ring cavity.
Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients (pts) with newly diagnosed glioblastoma (GBM)
2007-06-20

2000 Background: To evaluate safety, toxicity, and efficacy of the combination of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, in addition to standard temozolomide (TMZ) and radiotherapy (RT). Methods: 52 pts (PS 0–1: 92%, 2: 8%; median age 57 yrs) after tumor resection (n=43/83%) or biopsy (n= 9/17%) were treated with standard TMZ/RT (Stupp et al. NEJM 2005). In addition cilengitide (500 mg i.v., 2x/week) was started one week before TMZ/RT and given throughout for the duration of chemotherapy or until progression. The primary endpoint was progression free survival rate at 6 months (target: 65%). Pts were followed with MRI every 2 months. Histopathologic diagnosis and MRI imaging were independently reviewed, O 6 -Methylguanine- DNA methyltransferase (MGMT) promotor methylation status was assessed in 45 (86.5%) pts. Results: 46 pts (92%) completed RT, = 90% of concomitant TMZ was received by 42 pts and cilengitide by 45 pts. 20 pts (3 ongoing) completed 6 cycles of maintenance TMZ and cilengitide. Observed hematological grade 3 and 4 toxicities were: lymphopenia (28/52, 53.8%), thrombocytopenia (7/52 pt. 13.4%) and neutropenia (5/52, 9.6%). Treatment related non-hematologic grade 3/4 toxicities were reported for n=3/52 (5.7%) patients: constitutional symptoms (asthenia, fatigue, anorexia, n=3); elevated liver function tests (n=1), deep venous thrombosis and pulmonary embolism (n=1). One patient with a history of sigmoid diverticulosis experienced sigmoid perforation (grade 2). In total, 34/52 (65.4% [95% CI, 50.9–78.0%]) of the pts were progression free at 6 months. Pts with MGMT gene-promotor methylation in the tumor were more likely to reach 6 months PFS endpoint. Conclusions: The study reached its primary endpoint. The combination of the integrin inhibitor RGD peptide Cilengitide and TMZ/RT was well tolerated, PFS at 6 months is encouraging. MGMT gene promoter methylation correlates with outcome. At the time of ASCO, updated results and survival estimates after a minimum follow-up of at least 1 year will be available. [Table: see text]