julilili42/papers huggingface dataset:
The Use of Again in 19th‐Century English versus Present‐Day English
2009-05-22

Abstract. The central claim of this paper is that the use of the adverb again has changed between 19th‐century English and present‐day English. In particular, restitutive uses were more easily and generally available in the 19th century than they are now. This diachronic change provides evidence for a lexical parameter governing the behavior of adverbs at the syntax/semantics interface. The parameter relates surface form to possible interpretations and thus introduces an interesting notion of visibility into linguistic theory.
A global survey of the role of ultraviolet radiation and hormonal influences in the development of melasma
2009-05-26

The results suggest that, whilst accepted causes do affect onset of melasma, a combination of these factors often triggers this disorder. These factors may provide further insights into how physicians can manage individual melasma cases, support recommendation of preventative measures and even anticipate treatment results and recurrence.
Dramatic Shifts in Circulating CD4 but not CD8 T Cell Subsets in Mild Alzheimer's Disease
2009-05-26

The distribution of peripheral T cell subsets in young and healthy old people is markedly different, characterized by decreased numbers of naïve cells and increased numbers and clonal expansions of memory cells, predominantly in the CD8+ MHC class I-restricted subset. Here, however, we document dramatic alterations in naïve and memory subsets of CD4+ cells in patients with mild Alzheimer's disease (AD), with greatly decreased percentages of naïve cells, elevated memory cells, and increased proportions of CD4+ but not CD8+ cells lacking the important costimulatory receptor CD28. CD4+CD25(high) potentially T regulatory cells with a naïve phenotype are also reduced in AD patients. Together these data provide stronger evidence than hitherto presented for more highly differentiated CD4+ as well as CD8+ T cells in AD patients, consistent with an adaptive immune system undergoing persistent antigenic challenge and possibly manifesting dysregulation as a result.
Aging effects on human calf muscle properties assessed by MRI at 3 Tesla
2009-05-26

Abstract Purpose To determine age‐related changes in MR properties as T2 and T2* relaxation times, fat content, and magnetization transfer in the human calf, and comparison of these effects in different muscle groups. Materials and Methods Studies were performed on 12 “younger” (mean, 31.2 ± 6.1 years) and 11 “older” healthy adult individuals (mean, 66.1 ± 7.8 years). The tibialis anterior muscle, the soleus muscle and the gastrocnemius muscle were examined at rest in a 3 Tesla whole‐body MR unit. T2 and T2*, muscular fat content and magnetization transfer ratios (MTR) were determined. Results of the two age groups were compared, and differences between the muscle groups were investigated. Results Increase of T2 and muscular fat was detected with age with significant difference between the age groups. The extent of fatty infiltration was much more variable for the “older” group. For both age groups, the tibialis anterior muscle showed the lowest fat content with 1.2 ± 0.4% in the “young” group and 2.3 ± 0.7% in the “older” group. A strong correlation between fat content and T2 was found, while the groups did not significantly differ regarding T2*. Decrease in the MTR could only be shown for the tibialis anterior muscle with age. Conclusion Age‐related changes in healthy human calf musculature were found. Further studies might show possible correlations of age‐dependent changes with physical efficiency and susceptibility to diseases like type 2 diabetes. J. Magn. Reson. Imaging 2009;29:1346–1354. © 2009 Wiley‐Liss, Inc.
Decreased Plasma Levels of Granulocyte-Colony Stimulating Factor (G-CSF) in Patients with Early Alzheimer's Disease
2009-05-26

Alzheimer's disease (AD) is characterized by massive neuronal cell loss in the brain. Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. In the present study, we found significantly lower G-CSF plasma levels in 50 early AD patients in comparison with 50 age-matched healthy controls. In AD patients, G-CSF levels showed a significant inverse correlation with amyloid-beta (Abeta1-42) levels in cerebrospinal fluid, but not with levels of tau protein in cerebrospinal fluid or Mini-Mental Status Examination scores. In addition, G-CSF plasma levels were significantly inversely correlated with age in AD patients and healthy controls. In conclusion, decreased G-CSF plasma levels in early AD patients may contribute to a deficient hematopoietic brain support with putative pathogenic relevance. Further studies are needed to examine whether a modulation of hematopoietic growth factors such as G-CSF could be a promising new therapeutic strategy for AD.
Early Maastrichtian carbon cycle perturbation and cooling event: Implications from the South Atlantic Ocean
2009-05-26

Published stable isotope records in marine carbonate are characterized by a positive δ 18 O excursion associated with a negative δ 13 C shift during the early Maastrichtian. However, the cause and even the precise timing of these excursions remain uncertain. We have generated high‐resolution foraminiferal stable isotope and gray‐scale records for the latest Campanian to early Maastrichtian (∼73–68 Ma) at two Ocean Drilling Program sites, 525 (Walvis Ridge) and 690 (Weddell Sea). We demonstrate that the negative δ 13 C excursion is decoupled from the δ 18 O increase with a lag of about 600 ka. Our δ 13 C records (both planktic and benthic) show an amplitude for the negative excursion of 0.7‰ that falls between about 72.1 and 70.7 Ma. Our planktic δ 18 O records indicate an overall increase of 1.2‰ from 73 to 68 Ma at Site 690, whereas at Site 525 they record a slightly smaller increase (∼1‰) that peaks around 70.1 Ma with decreasing values thereafter. Our benthic δ 18 O data indicate an increase of ∼1.5‰ at Site 525 and ∼0.7‰ at Site 690 between about 71.4 and 69.9 Ma. Benthic δ 18 O values show different baseline values at the two sites before and after the excursion, but the larger increase at Site 525 means that the values attained at the peak of the excursion are similar at the two sites. We interpret this observation in terms of water mass changes. The excursion is interpreted to reflect a cooling of bottom waters in response to the strengthening contribution of intermediate‐ to deep‐water production in the high southern latitudes rather than increased ice volume. The associated carbon cycle perturbations that we observe are interpreted to reflect a weakening of surface water stratification and increased productivity, as supported by our gray value data.
Novel Application of Fluorescence Lifetime and Fluorescence Microscopy Enables Quantitative Access to Subcellular Dynamics in Plant Cells
2009-05-26

One-chromophore fluorescence lifetime microscopy, combined with wavelength-specific fluorescence microscopy, opens up new frontiers for in vivo dynamic and quantitative analysis of cellular processes at high resolution which are not addressable by pure imaging technologies or transmission electron microscopy.
Efficient Processing of Alzheimer's Disease Amyloid-Beta Peptides by Neuroectodermally Converted Mesenchymal Stem Cells
2009-05-26

Most disease-modifying therapeutic approaches in Alzheimer's disease (AD) aim to reduce the accumulation of neurotoxic amyloid-beta (Abeta) peptides as a hallmark of AD pathogenesis. Here we report the in vitro basis for a potential autologous stem cell-based strategy for widespread delivery of enzymatic activities against Abeta formation in the brain. We detected the functional induction of two genes upon neuroectodermal conversion of human adult mesenchymal stem cells (MSCs), namely F-spondin and neprilysin (CD10), with a 4,992 + or - 697-fold and 692 + or - 226-fold increase of mRNA levels in converted cells compared to MSCs, respectively (n = 3; P < 0.01). These genes are known to be involved in the formation and degradation of Abeta peptides, respectively. Consistently, coincubation of the neuroectodermally converted MSCs with HEK-293 cells stably expressing amyloid precursor protein (APP) lead to a significant cell dose-dependent decrease of Abeta peptides. These in vitro results indicate that MSCs might be useful vehicles for delivering anti-Abeta activity depicting a causal stem cell-based therapeutic approach to treat AD.
Ontogenetically stable dimorphism in a lacertid lizard (Acanthodactylus boskianus) with tests of methodology and comments on life-history
2009-05-26

Recent arguments in the literature prompted us to compare methods for assessing sexual dimorphism in body proportions of lacertid lizards, using Acanthodactylus boskianus. Although expressing body-part measurements as proportional to head length was the most effective method, we recommend using trunk length for the baseline as a general method for lizards. We also argue that, when aiming to assess sexual dimorphism in body proportions of lizards, if the context is ecological, all available adults should be included. However, for morphology and taxonomy, small sub-samples of the largest individuals that maximally express their genetic morphological potential should be used. In A. boskianus, the sexual dimorphism of mensural characters in adults was typical: males were larger, with relatively larger head and appendages. However, the ontogeny of this dimorphism was unusual in that the differences existed already in youth and thereafter persisted isometrically. The sexual dimorphism of meristic characters was male-biased in numbers of femoral pores and of caudal vertebrae, and female-biased in numbers of ventral plates along the trunk and of precaudal vertebrae. Size dimorphism may conceivably play a role in sex recognition because two potential visual cues (i.e. size dimorphism and dichromatism) appear to complement each other.
An apoptosis biomarker for prediction of nonalcoholic steatohepatitis #
2009-05-26

We read with interest the article by Feldstein et al. that evaluated the use of cytokeratin-18 (CK-18) fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis (NASH).1 The authors reported that plasma levels of an apoptosis-associated CK-18 fragment were significantly elevated in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) as compared to healthy individuals. Moreover, they observed significantly higher CK-18 fragment levels in NASH compared to "borderline diagnosis" or simple steatosis. The authors conclude that such noninvasive determination of CK-18 fragments allows the prediction of NASH and severity of disease in patients with NAFLD. Liver biopsy is still considered the gold standard for assessment of liver disease activity, although it remains associated with several disadvantages including high costs and risks of clinical complications. Noninvasive techniques that can monitor disease activity and distinguish NASH from simple steatosis are therefore urgently needed.2 The multicenter study by Feldstein and coworkers is therefore of great clinical importance. Caspase-generated CK-18 fragments are released during hepatocyte apoptosis, a fundamental process in virtually all acute and chronic liver diseases that are characterized by inflammation, steatosis, or fibrosis.3-6 Previous studies in patients with chronic HCV infection have shown that activation of hepatic caspases closely correlates with inflammation.7 In addition, detection of caspase-generated CK-18 fragments in sera from patients with chronic hepatitis C virus (HCV) infection has recently been associated with fibrotic liver injury.8 Another study showed a correlation of CK-18 fragment levels with the proportion of HCV-associated liver steatosis.9 In this latter study, only patients with minimal inflammatory disease activity and low stages of fibrosis were included, suggesting that even under conditions of mild inflammation, CK-18 fragment levels correlate with the extent of steatosis. Hepatocyte apoptosis and elevated CK-18 fragment levels are also prominent features of cholestatic liver diseases.10 Furthermore, presumably due to increased cell turnover, elevated serum levels of CK-18 fragments have been reported even in noncirrhotic hepatocellular carcinoma.10 In conclusion, CK-18 fragments represent a strong predictor and useful noninvasive biomarker for the diagnosis of NASH in well-defined patients. However, it should be taken into account that a variety of hepatic pathologies may result in elevated CK-18 fragment levels. Thus, this marker is not specific for NASH but rather a general indicator of severe liver disease. Heike Bantel*, Matthias J. Bahr*, Klaus Schulze-Osthoff , * Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany, Interfaculty Institute for Biochemistry, University of Tübingen, Tübingen, Germany.
ChemInform Abstract: Biosynthetic Capacities of Actinomycetes. Part 47. Nataxazole (I), a New Benzoxazole Derivative with Antitumor Activity Produced by Streptomyces sp. Tue 6176.
2009-05-26

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Superfluid signatures in magnetar seismology
2009-05-27

We investigate the role of neutron star superfluidity for magnetar oscillations. Using a plane-wave analysis, we estimate the effects of a neutron superfluid in the elastic crust region. We demonstrate that the superfluid imprint is likely to be more significant than the effects of the crustal magnetic field. We also consider the region immediately beneath the crust, where superfluid neutrons are thought to coexist with a type II proton superconductor. Since the magnetic field in the latter is carried by an array of fluxtubes, the dynamics of this region differ from standard magnetohydrodynamics. We show that the presence of the neutron superfluid (again) leaves a clear imprint on the oscillations of the system. Taken together, our estimates show that the superfluid components cannot be ignored in efforts to carry out 'magnetar seismology'. This increases the level of complexity of the modelling problem, but also points to the possibility of using observations to probe the superfluid nature of supranuclear matter.
Expression of Organic Cation Transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) Is Affected by Genetic Factors and Cholestasis in Human Liver†
2009-05-28

An important function of hepatocytes is the biotransformation and elimination of various drugs, many of which are organic cations and are taken up by organic cation transporters (OCTs) of the solute carrier family 22 (SLC22). Because interindividual variability of OCT expression may affect response to cationic drugs such as metformin, we systematically investigated genetic and nongenetic factors of OCT1/SLC22A1 and OCT3/SLC22A3 expression in human liver. OCT1 and OCT3 expression (messenger RNA [mRNA], protein) was analyzed in liver tissue samples from 150 Caucasian subjects. Hepatic OCTs were localized by way of immunofluorescence microscopy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and genome-wide single-nucleotide polymorphism microarray technology served to genotype 92 variants in the SLC22A1-A3/OCT1-3 gene cluster. Transport of metformin by recombinant human OCT1 and OCT3 was compared using transfected cells. OCT1 mRNA and protein expression varied 113- and 83-fold, respectively; OCT3 mRNA expression varied 27-fold. OCT1 transcript levels were on average 15-fold higher compared with OCT3. We localized the OCT3 protein to the basolateral hepatocyte membrane and identified metformin as an OCT3 substrate. OCT1 and OCT3 expression are independent of age and sex but were significantly reduced in liver donors diagnosed as cholestatic ( P ≤ 0.01). Several haplotypes for OCT1 and OCT3 were identified. Multivariate analysis adjusted for multiple testing showed that only the OCT1-Arg61Cys variant (rs12208357) strongly correlated with decreased OCT1 protein expression ( P &lt; 0.0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels ( P = 0.03). Conclusion: We identified cholestasis and genetic variants as critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression. This indicates consequences for hepatic elimination of and response to OCT substrates such as metformin. (Hepatology 2009.)
Individual Stearoyl-CoA Desaturase 1 Expression Modulates Endoplasmic Reticulum Stress and Inflammation in Human Myotubes and Is Associated With Skeletal Muscle Lipid Storage and Insulin Sensitivity In Vivo
2009-05-28

OBJECTIVE Increased plasma levels of free fatty acids occur in obesity and type 2 diabetes and contribute to the development of insulin resistance. Saturated fatty acids (SFAs) such as palmitate especially have lipotoxic effects leading to endoplasmatic reticulum (ER) stress, inflammation, and insulin resistance. Stearoyl-CoA desaturase 1 (SCD1) plays a key role in preventing lipotoxic effects, as it converts SFAs to less harmful monounsaturated fatty acids. Here, we tested the hypothesis that individual differences in the regulation of SCD1 expression by palmitate exist and influence insulin sensitivity and the cellular response to palmitate. RESEARCH DESIGN AND METHODS Palmitate-induced gene expression was studied in primary human myotubes of 39 metabolically characterized individuals, as well as in an SCD1-overexpressing cell culture model. RESULTS SCD1 mRNA expression and inducibility by palmitate in cultured myotubes showed a broad interindividual variation, presumably due to inheritable characteristics of the donors. Overexpression of SCD1 prevented the inflammatory and ER stress response to palmitate exposure. In primary human myotubes, high SCD1 inducibility was associated with a low inflammatory (interleukin [IL]-6, IL-8, and chemokine [CXC motif] ligand 3 [CXCL3]) and ER stress (CCAAT/enhancer binding protein [C/EBP] homologous protein, activating transcription factor 3 [ATF3], and X-box binding protein 1 [XBP1]) response to palmitate exposure. Finally, palmitate-stimulated SCD1 mRNA expression, positively correlated with intramyocellular lipid (IMCL) content of the donors, was measured by 1H-magnetic resonance spectroscopy. After adjustment for IMCL, SCD1 expression and inducibility were positively correlated with insulin sensitivity. CONCLUSIONS We hypothesize that myocellular SCD1 inducibility by palmitate is an individual characteristic that modulates lipid storage, palmitate-induced inflammation, ER stress, and insulin resistance. This may describe individuals with increased capability of innoxious free fatty acid handling and benign triglyceride storage.
Perfusion Imaging in Pusher Syndrome to Investigate the Neural Substrates Involved in Controlling Upright Body Position
2009-05-28

Brain damage may induce a dysfunction of upright body position termed "pusher syndrome". Patients with such disorder suffer from an alteration of their sense of body verticality. They experience their body as oriented upright when actually tilted nearly 20 degrees to the ipsilesional side. Pusher syndrome typically is associated with posterior thalamic stroke; less frequently with extra-thalamic lesions. This argued for a fundamental role of these structures in our control of upright body posture. Here we investigated whether such patients may show additional functional or metabolic abnormalities outside the areas of brain lesion. We investigated 19 stroke patients with thalamic or with extra-thalamic lesions showing versus not showing misperception of body orientation. We measured fluid-attenuated inversion-recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI). This allowed us to determine the structural damage as well as to identify the malperfused but structural intact tissue. Pusher patients with thalamic lesions did not show dysfunctional brain areas in addition to the ones found to be structurally damaged. In the pusher patients with extra-thalamic lesions, the thalamus was neither structurally damaged nor malperfused. Rather, these patients showed small regions of abnormal perfusion in the structurally intact inferior frontal gyrus, middle temporal gyrus, inferior parietal lobule, and parietal white matter. The results indicate that these extra-thalamic brain areas contribute to the network controlling upright body posture. The data also suggest that damage of the neural tissue in the posterior thalamus itself rather than additional malperfusion in distant cortical areas is associated with pusher syndrome. Hence, it seems as if the normal functioning of both extra-thalamic as well as posterior thalamic structures is integral to perceiving gravity and controlling upright body orientation in humans.
Cholesky-decomposed densities in Laplace-based second-order Møller–Plesset perturbation theory
2009-05-28

Based on our linear-scaling atomic orbital second-order Møller–Plesset perturbation theory (AO-MP2) method [J. Chem. Phys. 130, 064107 (2009)], we explore the use of Cholesky-decomposed pseudodensity (CDD) matrices within the Laplace formulation. Numerically significant contributions are preselected using our multipole-based integral estimates as upper bounds to two-electron integrals so that the 1/R6 decay behavior of transformed Coulomb-type products is exploited. In addition, we combine our new CDD-MP2 method with the resolution of the identity (RI) approach. Even though the use of RI results in a method that shows a quadratic scaling behavior in the dominant steps, gains of up to one or two orders of magnitude vs. our original AO-MP2 method are observed in particular for larger basis sets.
Diffusion-Driven Device for a High-Resolution Dose−Response Profiling of Combination Chemotherapy
2009-05-28

Combination therapies have proven vital in the fight against HIV and cancer. However, the identification and optimization of such combination therapies is largely experience driven and an activity of clinicians rather than of systematic screening efforts. Here we present a diffusion device, compatible with the format of a 12-well microtiter plate, to create and test all possible mixtures of two substances with only two pipetting steps. Applications to the testing of different drug combinations and the parallel screening of different leukemia cell lines as well as primary patient cells are presented. The diffusion device yields qualitatively and quantitatively comparable results to an MTT viability assay conducted in a standard 96-well format albeit with a tremendous reduction of processing steps. In addition, a fluorescence-based annexin V binding assay of cell death was implemented. Next to the reduction of processing steps, the diffusion device constitutes a considerable assay miniaturization that overcomes the problems typically associated with miniaturization as a consequence of small sample volumes. Given its ease of handling, the device will greatly advance the development and optimization of combination drugs and the identification of optimum drug combinations in personalized medicine.