julilili42/papers huggingface dataset:
Myonuclear Degeneration in LMNA Null Mice
2008-03-27

Abstract Lamins A/C, the major constituent of the nuclear lamina, confer mechanical stability to nuclei. We examined the myonuclei of LMNA null mice at the myotendinous junctions (MTJ), the site of longitudinal force transmission from contractile proteins to extracellular proteins. The right soleus and rectus femoris muscles of five null mutants aged 5–7 weeks and two wild‐type animals aged 5 weeks and 6 months were examined by electron microscopy. The myofibers merging into the tendons were assessed for nuclear disintegration and cytoplasmic degeneration. The myofibers of the wild‐type rectus femoris and soleus muscles revealed 19–27 nuclei/50 myofibers and 5–8/20, respectively, with no signs of degeneration. The rectus femoris muscle fibers of the null mice contained 75–117 myonuclei/50 myofibers, the soleus muscle, 13–36 nuclei/20 myofibers. Eleven to twenty‐one per 50 myonuclei of the rectus femoris myonuclei showed chromatin clumping, nuclear fragmentation, nuclear inclusions and invaginations, and intranuclear filaments. The values were 12–19/50 for the soleus myonuclei. Moreover, 5–12/50 rectus femoris myofibers and 5–14/20, of the soleus myofibers showed cytoplasmic degeneration. None of these changes was found distal to the MTJ. These results favor the notion that myonuclei lacking a functional lamina are susceptible to mechanical stress in vivo . These alterations may contribute to the development of early joint contractures, a feature of ADEDMD.
A mixture model of nuchal translucency thickness in screening for chromosomal defects
2008-03-28

Abstract Objective Fetal nuchal translucency (NT) thickness increases with crown–rump length (CRL). In screening for chromosomal defects patient‐specific risks are derived by multiplying the a priori maternal age‐related risk by a likelihood ratio, determined from the deviation of the measured NT from the expected median. To quantify this deviation the measured NT is either subtracted (delta NT) or divided by the expected median (multiple of the median method, MoM). This study examines the validity of these methods. Methods NT was prospectively measured at 11 + 0 to 13 + 6 weeks in screening for chromosomal defects. The distribution of NT in euploid and chromosomally abnormal fetuses was examined. Results There were 37 078 normal pregnancies and 264 with trisomy 21, 81 with trisomy 18, 38 with trisomy 13 and 27 with Turner syndrome. We found that firstly, contrary to the assumption underlying the delta NT method, the distribution of delta NT changes with CRL and secondly, contrary to the assumption underlying the MoM method the distribution of NT was not Gaussian. Fetal NT followed two distributions, one that was dependent on CRL and one that was independent of CRL. The distribution in which NT increases with CRL was observed in about 95% of euploid fetuses, 5% with trisomy 21, 30% with trisomy 18, 15% with trisomy 13 and 10% with Turner syndrome. The median CRL‐independent NT was 2.0 mm for the euploid group and 3.4, 5.5, 4.0 and 7.8 mm for trisomies 21, 18, 13 and Turner syndrome, respectively. Conclusions The NT thickness in chromosomally normal and abnormal fetuses follows a mixture of a gestation‐dependent and gestation‐independent distribution. Copyright © 2008 ISUOG. Published by John Wiley &amp; Sons, Ltd.
Influence of Boron and Carbon on the Oxidation of Smtered Silicon Carbide at 1500°C
2008-03-28

Sintered Silicon Carbide (SSiC) with varying boron and carbon sintering additive contents were oxidized a t 1500°C in dry and humid environment. Increasing bubble and pit formation was observed with increasing boron carbide (B4C) content. The bubble generation is due to low viscosity, borosilicate droplets in the oxide scale and a gas pressure above atmospheric pressure. Thermochemical calculations revealed that the gas pressure is caused by B4C oxidation beneath the oxide scale. The bubble appearance changed with addition of water to the oxygen atmosphere, because humidity changes the viscosity of the borosilicate glass and a higher gas pressure is generated a t the substrate-scale interface.
Isoxazolone Based Inhibitors of p38 MAP Kinases
2008-03-29

SAR of N-alkylated isoxazolones as p38 MAP kinase inhibitors was realized. The data herein show the possibility of transferring the SAR study and evaluation from N-1-substituted imidazole to isoxazolones. Optimization of substituent was realized.
Non-Classical Interacting Random Walks
2008-03-31

The workshop was organized by Francis Comets (Paris 7) and Martin Zerner (Tübingen). It was attended by fifty participants of about twenty different nationalities. Among the participants was a relatively large number of young researchers, some of which were supported by the European Union within the Marie Curie Conferences Programme and by the National Science Foundation. The title of the workshop was Non-Classical Interacting Random Walks . The study of random walks (RWs) goes back to the beginnings of probability theory in the seventeenth century. Some of the first probabilists like Bernoulli and Pascal investigated the properties of coin tossing sequences and other simple games of chance, which nowadays are modeled by RWs. Such a RW takes steps at fixed time intervals, and at each step a random direction is chosen, which gives a chaotic trajectory. So in their most stringent definition, RWs come up as sums of independent and identically distributed random variables with real or often integer lattice values. A somewhat wider definition includes time-homogeneous Markov chains whose transition probabilities are in some way adapted to a given geometric-algebraic-combinatorial structure of the underlying state space. In this context, many tools from potential theory, graph theory, harmonic analysis and Fourier analysis are available. The focus of this workshop was on a quite different area of current research on RWs. This is what the term “non-classical” in the title refers to. Some of the RWs, which are currently heavily investigated, are quite “irregular”: Some are not Markovian, but are influenced by their own past. Others are Markovian, but interact with a possibly random environment, which influences the transitions of the walk. Many of the tools used in the more traditional settings of RWs fail in this context. The main models considered in this workshop were RWs in random environments (RWRE) with talks mainly on Monday, RWs in random potential and random polymers on Tuesday, excited RWs on Wednesday morning, followed by an exciting open problem session in the evening, reinforced RWs on Thursday and various other RWs on Friday. The programme consisted in total of 23 talks of about 50 minutes each and the open problem session. On most days a long lunch break from 12:30 to 16:00 gave plenty of opportunity for interaction between the participants. Following the reinforcement by previous workshops and in spite of the title of the current workshop, on Wednesday afternoon most participants took part in the classical interacting non-random walk to St. Roman.
Aging of the Immune System as a Prognostic Factor for Human Longevity
2008-04-01

Accumulating data are documenting an inverse relationship between immune status, response to vaccination, health, and longevity, suggesting that the immune system becomes less effective with advancing age and that this is clinically relevant. The mechanisms and consequences of age-associated immune alterations, designated immunosenescence, are briefly reviewed here.
Dexamethasone Concentration Gradients Along Scala Tympani After Application to the Round Window Membrane
2008-04-01

The existence of substantial basal-apical concentration gradients of Dex-P in ST perilymph were demonstrated experimentally. If the variability in peak concentration and gradient is also present under clinical conditions, this may contribute to the heterogeneity of outcome that is observed after intratympanic application of glucocorticoids for various inner ear diseases.
Reduced V-ATPase Activity in thetrans-Golgi Network Causes Oxylipin-Dependent Hypocotyl Growth Inhibition inArabidopsis
2008-04-01

Abstract Regulated cell expansion allows plants to adapt their morphogenesis to prevailing environmental conditions. Cell expansion is driven by turgor pressure created by osmotic water uptake and is restricted by the extensibility of the cell wall, which in turn is regulated by the synthesis, incorporation, and cross-linking of new cell wall components. The vacuolar H+-ATPase (V-ATPase) could provide a way to coordinately regulate turgor pressure and cell wall synthesis, as it energizes the secondary active transport of solutes across the tonoplast and also has an important function in the trans-Golgi network (TGN), which affects synthesis and trafficking of cell wall components. We have previously shown that det3, a mutant with reduced V-ATPase activity, has a severe defect in cell expansion. However, it was not clear if this is caused by a defect in turgor pressure or in cell wall synthesis. Here, we show that inhibition of the tonoplast-localized V-ATPase subunit isoform VHA-a3 does not impair cell expansion. By contrast, inhibition of the TGN-localized isoform VHA-a1 is sufficient to restrict cell expansion. Furthermore, we provide evidence that the reduced hypocotyl cell expansion in det3 is conditional and due to active, hormone-mediated growth inhibition caused by a cell wall defect.
Biogeochemistry and Community Composition of Iron- and Sulfur-Precipitating Microbial Mats at the Chefren Mud Volcano (Nile Deep Sea Fan, Eastern Mediterranean)
2008-04-01

ABSTRACT In this study we determined the composition and biogeochemistry of novel, brightly colored, white and orange microbial mats at the surface of a brine seep at the outer rim of the Chefren mud volcano. These mats were interspersed with one another, but their underlying sediment biogeochemistries differed considerably. Microscopy revealed that the white mats were granules composed of elemental S filaments, similar to those produced by the sulfide-oxidizing epsilonproteobacterium “ Candidatus Arcobacter sulfidicus.” Fluorescence in situ hybridization indicated that microorganisms targeted by a “ Ca . Arcobacter sulfidicus”-specific oligonucleotide probe constituted up to 24% of the total the cells within these mats. Several 16S rRNA gene sequences from organisms closely related to “ Ca . Arcobacter sulfidicus” were identified. In contrast, the orange mat consisted mostly of bright orange flakes composed of empty Fe(III) (hydr)oxide-coated microbial sheaths, similar to those produced by the neutrophilic Fe(II)-oxidizing betaproteobacterium Leptothrix ochracea . None of the 16S rRNA gene sequences obtained from these samples were closely related to sequences of known neutrophilic aerobic Fe(II)-oxidizing bacteria. The sediments below both types of mats showed relatively high sulfate reduction rates (300 nmol·cm −3 ·day −1 ) partially fueled by the anaerobic oxidation of methane (10 to 20 nmol·cm −3 ·day −1 ). Free sulfide produced below the white mat was depleted by sulfide oxidation within the mat itself. Below the orange mat free Fe(II) reached the surface layer and was depleted in part by microbial Fe(II) oxidation. Both mats and the sediments underneath them hosted very diverse microbial communities and contained mineral precipitates, most likely due to differences in fluid flow patterns.
The topoisomerase II inhibitor, genistein, induces G2/M arrest and apoptosis in human malignant glioma cell lines
2008-04-01

The protein tyrosine kinase inhibitor, genistein, has been reported to inhibit proliferation and to induce cell death in various non-solid and solid cancer cell lines. Herein, we examined the effects of genistein in several human malignant glioma cell lines. We found that genistein inhibited the proliferation of LN-18, LNT-229, LN-308 and T98G cells at EC50 concentrations of 25-80 microM (72 h of exposure). The growth of a non-neoplastic immortalized human astrocyte cell line, SV-FHAS, was inhibited at similar concentrations. There was a reduction in [3H]-methylthymidine incorporation and a moderate lactate dehydrogenase release as a sign of cell death in genistein-treated glioma cells. Electron microscopy showed morphological changes with mitochondrial swelling and apoptosis in glioma cells treated with high concentrations of genistein. Genistein-induced cytotoxicity was associated with an increased DNA/topoisomerase II complex formation. Furthermore, genistein induced cell cycle arrest in G2/M. There was an increase in the p53 and p21 levels in response to genistein. However, there was no difference in genistein sensitivity between p21-deficient colon carcinoma cells and isogenic control cells. Genistein-induced cell death in LN-18 and LNT-229 was unaffected by the ectopic expression of the preferential caspase 1/8 inhibitor, crm-A, or co-exposure to the pan-specific pseudosubstrate caspase inhibitor, zVAD-fmk. The ectopic expression of the anti-apoptotic BCL-2 protein attenuated the cytotoxic effects of genistein. Moreover, the ectopic expression of temperature-sensitive p53V135A, which acts as a dominant-negative p53 mutant at 38.5 degrees C but assumes p53 wild-type properties at 32.5 degrees C, in LN-18 or LNT-229 cells, had no effect on genistein cytotoxicity at either temperature. Genistein did not act in synergy with CD95 ligand-induced apoptosis or various cancer chemotherapy drugs in cytotoxic or clonogenic cell death assays. Thus, genistein-like protein kinase inhibitors are promising agents for the experimental treatment of malignant gliomas.
Evidence-based and interdisciplinary consensus-based German guidelines: systemic medical treatment of melanoma in the adjuvant and palliative setting
2008-04-01

Systemic medical treatment of melanoma is administered in the adjuvant and palliative setting. Adjuvant therapy may be considered in patients with primary melanoma with more than 1.5 mm tumor thickness and with regional node metastasis. Presently no indication for systemic adjuvant chemotherapy or for adjuvant therapy with nonspecific immune-stimulatory agents outside controlled studies is seen. Interferon-alpha is the first substance in the adjuvant therapy of melanoma, which has shown to present a significant advantage to the patients in some prospective randomized studies. Good arguments for using adjuvant interferon-alpha therapy in high-risk melanoma patients exist. Both high-dose and low-dose interferon-alpha show promise. The major indications for systemic chemotherapy and chemoimmunotherapy are inoperable recurrent tumors, inoperable regional metastases and distant metastases (stage IV). As treatment in such situations is primarily palliative, the effect of any regimen on the quality of life must be carefully weighed. As a first line treatment, single agent therapy is recommended, as polychemotherapy or biochemotherapy did not show significant advantages for prolongation of survival; hence they are more toxic. An urgent need for development of new treatment modalities is necessary and general principles of experimental immunotherapy are outlined.
A Cryptic Vascular Endothelial Growth Factor T-Cell Epitope: Identification and Characterization by Mass Spectrometry and T-Cell Assays
2008-04-01

Abstract Vascular endothelial growth factor (VEGF) is involved in various physiologic processes, such as angiogenesis or wound healing, but is also crucial in pathologic events, such as tumor growth. Thus, clinical anti-VEGF treatments have been developed that could already show beneficial effects for cancer patients. In this article, we describe the first VEGF-derived CD8+ T-cell epitope. The natural HLA ligand SRFGGAVVR was identified by differential mass spectrometry in two primary renal cell carcinomas (RCC) and was significantly overpresented on both tumor tissues. SRFGGAVVR is derived from a cryptic translated region of VEGF presumably by initiation of translation at the nonclassic start codon CUG499. SRFGGAVVR-specific T cells were generated in vitro using peptide-loaded dendritic cells or artificial antigen-presenting cells. SRFGGAVVR-specific CD8+ T cells, identified by HLA tetramer analysis after in vitro stimulation, were fully functional T effector cells, which were able to secrete IFN-γ on stimulation and killed tumor cells in vitro. Additionally, we have quantitatively analyzed VEGF mRNA and protein levels in RCC tumor and normal tissue samples by gene chip analysis, quantitative reverse transcription-PCR, in situ hybridization, and bead-based immunoassay. In the future, T cells directed against VEGF as a tumor-associated antigen may represent a possible way of combining peptide-based anti-VEGF immunotherapy with already existent anti-VEGF cancer therapies. [Cancer Res 2008;68(7):2447–54]
Prediction Error of the Multivariate Chain Ladder Reserving Method
2008-04-01

Abstract In this paper we consider the claims reserving problem in a multivariate context: that is, we study the multivariate chain-ladder (CL) method for a portfolio of N correlated runoff triangles based on multivariate age-to-age factors. This method allows for a simultaneous study of individual runoff subportfolios and facilitates the derivation of an estimator for the mean square error of prediction (MSEP) for the CL predictor of the ultimate claim of the total portfolio. However, unlike the already existing approaches we replace the univariate CL predictors with multivariate ones. These multivariate CL predictors reflect the correlation structure between the subportfolios and are optimal in terms of a classical optimality criterion, which leads to an improvement of the estimator for the MSEP. Moreover, all formulas are easy to implement on a spreadsheet because they are in matrix notation. We illustrate the results by means of an example.
ApoB100,LDLR−/−Mice Exhibit Reduced Electroretinographic Response and Cholesteryl Esters Deposits in the Retina
2008-04-01

The exclusive expression of apoB100 in LDL receptor-null mouse altered the ERG profile, without modifying the visual cycle of retinoids and led to cholesterol deposition in the retina. These findings clearly suggest the role of cholesterol metabolism in the functioning of the retina and possibly in the etiology of ocular diseases, including age-related macular degeneration.
The CpG Island Methylator Phenotype Correlates with Long-Range Epigenetic Silencing in Colorectal Cancer
2008-04-01

Abstract The CpG island methylator phenotype (CIMP), characterized by an exceptionally high frequency of methylation of discrete CpG islands, is observed in 18% to 25% of sporadic colorectal cancers. Another hypermethylation pattern found in colorectal cancers, termed long-range epigenetic silencing, is associated with DNA/histone methylation in three distinct gene clusters at chromosome 2q14.2, showing that DNA hypermethylation can span larger chromosomal domains and lead to the silencing of flanking, unmethylated genes. We investigated whether these two phenotypes are interrelated in colorectal cancers. The CIMP status of 148 sporadic colorectal cancers was determined by methylation-specific PCR. We determined the BRAF V600E mutation by mutant allele–specific PCR amplification. The methylation status of the MLH1 gene and of three CpG islands (EN1, SCTR, and INHBB), corresponding to three distinct clusters along 2q14.2, was determined by methylation-specific PCR. The average number of sites showing methylation in CIMP+ tumors was 2.21, compared with 1.22 for CIMP− individuals, and this difference was highly significant (P = 3.6 × 10−8, Mann-Whitney test). Moreover, all CIMP+ tumors showed hypermethylation of at least one of these loci, in contrast to CIMP− tumors, where 18 (16%) samples remained unmethylated. The mean number of simultaneously hypermethylated CpG islands at 2q14.2 differs significantly between CIMP− and CIMP+ tumors, suggesting varying effects of domain silencing in this region. Given that the number of hypermethylated loci at 2q14.2 likely affects the range of silenced flanking genes, high frequency of simultaneous hypermethylation of three CpG islands (EN1, SCTR, and INHBB) may have potential influence on specific characteristics of CIMP+ colorectal cancers. (Mol Cancer Res 2008;6(4):585–91)
Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial
2008-04-01

SUMMARY Tea preparations from the herb Artemisia annua L. (Aa) which is used in traditional Chinese medicine might offer an inexpensive way of producing artemisinin drugs locally. We compared Aa with sulfadoxine-pyrimethamine (SP) in the treatment of uncomplicated falciparum malaria in semi-immune adults. After seven days, the cure rate was 7/10 for the Aa compared to 7/9 for SP; this dropped to 4/10 for Aa and 4/9 for SP at day 14 and to 1/9 for Aa and 3/8 for SP at day 28.
Refinement of the MYP3 locus on human chromosome 12 in a German family with Mendelian autosomal dominant high-grade myopia by SNP array mapping
2008-04-01

Myopia, or short-sightedness, is the most common form of vision disorder worldwide. Higher levels of myopia, usually defined as an axial eye length of >26 mm or a refractive error of < -5.00 diopters are often designated as 'pathologic' myopia, because of the predisposition to develop further eye disorders such as retinal detachment, macular degeneration, cataract, or glaucoma. Many distinct forms of autosomal dominant non-syndromic high-grade myopia are described in humans. While the underlying chromosomal locations and critical disease intervals have been identified and located to physical map positions, the gene defects and causative mutations responsible for autosomal dominant myopia remain elusive to date. Examination of a German six-generation kindred by 10K whole genome chips led to the identification of a 19-cM map segment as being the most likely familial myopia candidate region spanning from chromosomal band 12q14.3 to 12q21.31 (MYP3). In our family, a maximum multi-point LOD score of 3.9 was obtained between rs1373877 and rs717996. The recombination breakpoints in this family and the interval of the originally reported German/Italian family defining the MYP3 locus on chromosome 12 (OMIM 603221, two-point LOD score 3.85 for markers D12S1706 and D12S327 at 12q21-23) allowed us to significantly refine a minimum consensus region. This new composite region is located between microsatellite marker D12S1684 at 75.8 K and SNP_A-1509586 (alias rs717996) at position 82,636,288 bp, and narrows the original 30.1 cM of the MYP3 interval to 6.8 cM. The refined MYP3 interval allowed us to restrict the list of database-indexed genes to 25, several of which are promising MYP3 candidates based on similarities with genes and proteins involved in vision physiology and eye disease. While autosomal dominant high-grade myopia is recognized to be genetically heterogeneous, our results suggest genetic homogeneity of the MYP3-based condition in families that share the same ethnic and geographical background. The future identification of this MYP3 gene may provide insights into the pathophysiology of myopia and eye development.
Cholecystokinin-58 is more potent in inhibiting food intake than cholecystokinin-8 in rats
2008-04-01

CCK-58 has the same potency in inhibiting food intake as CCK-8 in rats, but inhibits food intake longer. This might be due to its tertiary structure resulting in a delayed plasma degradation or a prolonged binding at the CCK receptor. As CCK-58 is the major CCK form in the gut wall and possibly in the circulating blood in humans, the effects of CCK on food intake might have been underestimated in the past.
Disruption of the Costal Margin with Transdiaphragmatic Abdominal Herniation Induced by Coughing
2008-04-01

We present a case of disruption of the cartilage of the costal margin resulting in herniation of abdominal contents across the diaphragm into the chest and across a gap between the ribs into the subcutaneous tissues. The literature on this condition and its management is reviewed.