gebhart/patrepeval huggingface dataset:
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study (2005)

The accumulation of lysosomes and their hydrolases within neurons is a well-established neuropathologic feature of Alzheimer disease (AD). Here we show that lysosomal pathology in AD brain involves extensive alterations of macroautophagy, an inducible pathway for the turnover of intracellular constituents, including organelles. Using immunogold labeling with compartmental markers and electron microscopy on neocortical biopsies from AD brain, we unequivocally identified autophagosomes and other prelysosomal autophagic vacuoles (AVs), which were morphologically and biochemically similar to AVs highly purified from mouse liver. AVs were uncommon in brains devoid of AD pathology but were abundant in AD brains particularly, within neuritic processes, including synaptic terminals. In dystrophic neurites, autophagosomes, multivesicular bodies, multilamellar bodies, and cathepsin-containing autophagolysosomes were the predominant organelles and accumulated in large numbers. These compartments were distinguishable from lysosomes and lysosomal dense bodies, previously shown also to be abundant in dystrophic neurites. Autophagy was evident in the perikarya of affected neurons, particularly in those with neurofibrillary pathology where it was associated with a relative depletion of mitochondria and other organelles. These observations provide the first evidence that macroautophagy is extensively involved in the neurodegenerative/regenerative process in AD. The striking accumulations of immature AV forms in dystrophic neurites suggest that the transport of AVs and their maturation to lysosomes may be impaired, thereby impeding the suspected neuroprotective functions of autophagy.
A sensitive method for the detection of beta-galactosidase in transfected mammalian cells. (1991)

A sensitive method has been developed for the detection of E. coli beta-galactosidase in transfected HeLa cells. The chromogenic substrate, CPRG (chlorophenol red-beta-D-galactopyranoside), was compared with ONPG (o-nitrophenyl-beta-D-galactopyranoside) by kinetic analysis with purified beta-galactosidase. The Km for CPRG was 1.35 mM and the Vmax was 21.4, whereas the Km for ONPG was 2.42 and the Vmax was 41.1. CPRG at 8.0 mM (6-fold Km) gave 86% of the Vmax and was used as the standard concentration for quantitation of enzyme levels. The Vmax for CPRG was half that for ONPG, and chlorophenol red has an extinction coefficient that is 21-fold higher than o-nitrophenol; these factors make CPRG about 10-fold greater in sensitivity for the quantitation of enzyme levels. The use of Nonidet P-40 to lyse the cells and the use of CPRG as substrate permitted the rapid detection of low levels of enzyme production from transfected human cells that could not be detected using ONPG.
Spine loss and other dendritic abnormalities in epilepsy (2000)

Studies of neurons from human epilepsy tissue and comparable animal models of focal epilepsy have consistently reported a marked decrease in dendritic spine density on hippocampal and neocortical pyramidal cells. Spine loss is often accompanied by focal varicose swellings or beading of dendritic segments. An ongoing excitotoxic injury of dendrites (dendrotoxicity), produced by excessive release of glutamate during seizures, is often assumed to produce these abnormalities. Indeed, application of glutamate receptor agonists to dendrites can produce both spine loss and beading. However, the cellular mechanisms underlying the two processes appear to be different. One recent study suggests NMDA-induced spine loss is produced by Ca2+-mediated alterations of the spine cytoskeleton. In contrast, dendritic beading is not dependent on extracellular Ca2+; instead, it appears to be produced by the movement of Na+ and Cl- intracellularly and an obligate movement of water to maintain osmolarity. A decrease in dendritic spine density was recently reported in a model of recurrent focal seizures in early life. Unlike results from other models, dendritic beading was not observed, and other signs of neuronal injury and death were absent. Thus, additional mechanisms to those of excitotoxicity may produce dendritic spine loss in epileptic tissue. A hypothesis is presented that spine loss can be a product of a partial deafferentation of pyramidal cells, resulting from an activity-dependent pruning of neuronal connectivity induced by recurring seizures. The dendritic abnormalities observed in epilepsy are commonly suggested to be a product and not a cause of epilepsy. However, anatomical remodeling may be accompanied by alterations in molecular expression and targeting of both voltage- and ligand-gated channels in dendrites. It is conceivable that such changes could contribute to the neuronal hyperexcitability of epilepsy.
Effect of Iberian × Duroc genotype on composition and sensory properties of dry‐cured ham (2007)

Abstract BACKGROUND: Dry‐cured ham quality from three different Iberian × Duroc genotypes was studied: GEN1, Iberian × Duroc1; GEN2, Duroc1 × Iberian; GEN3, Duroc2 × Iberian. GEN1 and GEN2 are reciprocal crosses, while the difference between GEN2 and GEN3 is the Duroc sire line. The line Duroc1 (DU1) was selected for the manufacture of dry‐cured meat products, whereas the line Duroc2 (DU2) was selected for meat production with low carcass fat. RESULTS: Dry‐cured hams from all genotypes had similar chemical composition. However, intramuscular fat of dry‐cured hams from GEN3 was more unsaturated than that from GEN2, while GEN1 was intermediate. Lipid oxidation, measured as 2‐thiobarbituric acid‐reactive substances (TBARS) and hexanal content, was similar between genotypes. The colour of hams was affected by genotype; hams from GEN2 showed higher lightness (CIE L *), while those from GEN3 had a less intense colour (lower a * and C *). Texture measured instrumentally did not differ between genotypes; however, in the sensory analysis, panellists considered hams from GEN3 more fibrous, while those from GEN2 were considered juicier. Hams from GEN3 were also perceived as saltier and more acid. CONCLUSION: Genotype affected the quality of Iberian hams, with those from GEN3 being of lower quality, and this genotype was considered less suitable for the manufacture of Iberian dry‐cured ham. Copyright © 2007 Society of Chemical Industry
Fast quantification of nucleic acid hybrids by affinity-based hybrid collection (1986)

A hybridization technique for the quantification of nucleic acids is described. In the method a probe pair is allowed to form hybrids with the target nucleic acid in solution. One of the probes has been modified with an affinity label, by which the formed hybrids can be isolated after the reaction. Streptavidin-agarose was used to capture hybrids containing biotinylated DNA. The hybrids were measured using radioiodine as label on the second probe. The rate of the hybridization reaction in solution is fast, allowing the whole procedure to be carried out in 3 h. The method is quantitative with a detection limit of 4 X 10(5) molecules (0.67 attomoles) target DNA. The test is insensitive to impurities in biological samples, which are analyzed without purification of the target DNA. Non-isotopic measurement of the hybrids can also be applied. In this case the hybrids are bound to microtitration wells and detected spectrophotometrically by peroxidase-catalyzed colour development.
Immune‐privileged embryonic Swiss mouse STO and STO cell‐derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines (2006)

Embryonic mouse STO (S, SIM; T, 6-thioguanine resistant; O, ouabain resistant) and 3(8)21-enhanced green fluorescent protein (EGFP) cell lines exhibit long-term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non-immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I- and class II-negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H-2K, H-2D, H-2L and I-A proteins were reassessed by reverse transcriptase-polymerase chain reaction (RT-PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT-PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)-gamma]-treated cultures. Despite prior PCR genotyping analyses suggestive of H-2q haplotypes in STO, 3(8)21-EGFP and parental 3(8)21 cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2K(d) determinants. In contrast, apart from H-2L(d[LOW]) display in 3(8)21 cells, H-2Dd, H-2Ld and I-Ad determinants were undetectable. All three lines expressed constitutive and cytokine-inducible CD34; however, except for inducible CD117([LOW]) expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD90.1 or CD95L/CD178 was observed. Constitutive and cytokine-inducible CD95([LOW]) expression was detected in STO and 3(8)21 cells, but not in 3(8)21-EGFP cells. MHC (class I(+[LOW])/class II-) and CD (CD34+/CD80-/CD86-/CD95L-) expression patterns in STO and STO cell-derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with mechanisms that are regulatory of immune privilege or functional tissue-specific plasticity is unknown.
Dermatology Life Quality Index (DLQI)-a simple practical measure for routine clinical use (1994)

A simple practical questionnaire technique for routine clinical use, the Dermatology Life Quality Index (DLQI) is described. One hundred and twenty patients with different skin diseases were asked about the impact of their disease and its treatment on their lives; a questionnaire, the DLQI, was developed based on their answers. The DLQI was then completed by 200 consecutive new patients attending a dermatology clinic. This study confirmed that atopic eczema, psoriasis and generalized pruritus have a greater impact on quality of life than acne, basal cell carcinomas and viral warts. The DLQI was also completed by 100 healthy volunteers; their mean score was very low (1.6%, s.d. 3.5) compared with the mean score for the dermatology patients (24.2%, s.d. 20.9). The reliability of the DLQI was examined in 53 patients using a 1 week test-retest method and reliability was found to be high (gamma s = 0.99).
Molecular Pathogenesis of Bernard-Soulier Syndrome (2000)

Bernard-Soulier syndrome (BSS), a hereditary qualitative platelet disorder, is now proved to be caused by a qualitative or quantitative abnormality of the platelet glycoprotein (GP) Ib/IX/V complex. We investigated the genetic background of two Japanese females with BSS and identified the molecular defects underlying this disease. The first case was a single base pair deletion within seven adenine repeats at position 4464-4470 (EMBL, no. M22403) of the GPIbalpha gene resulting in a frameshift and a premature stop codon. The second case was a single T-->C substitution at nucleotide 1856 (EMBL, no. M80478) of the GPIX gene resulting in Phe55(TTT)-->Ser(TCT) substitution. The latter case is of interest in considering the pathogenesis of BSS, because all four GPs consisting of the GPIb/IX/V complex have the same structural unit called leucine-rich repeat (LRR). Because this mutation is located within the LRR of the GPIX polypeptide, Phe55-->Ser substitution may result in an alteration of the LRR that leads to impaired surface expression of the GPIb/IX/V complex. To clarify the effect of this mutation on surface expression of the GPIb/IX complex, we performed transfection studies with a plasmid having this mutation. Mutant GPIX could not increase surface expression of the GPIb/IX complex, thus demonstrating an important role of the LRR of the GPIX polypeptide during biosynthesis.
Precision genome engineering with programmable DNA-nicking enzymes (2012)

Zinc finger nucleases (ZFNs) are powerful tools of genome engineering but are limited by their inevitable reliance on error-prone nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs), which gives rise to randomly generated, unwanted small insertions or deletions (indels) at both on-target and off-target sites. Here, we present programmable DNA-nicking enzymes (nickases) that produce single-strand breaks (SSBs) or nicks, instead of DSBs, which are repaired by error-free homologous recombination (HR) rather than mutagenic NHEJ. Unlike their corresponding nucleases, zinc finger nickases allow site-specific genome modifications only at the on-target site, without the induction of unwanted indels. We propose that programmable nickases will be of broad utility in research, medicine, and biotechnology, enabling precision genome engineering in any cell or organism.
An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis (2007)

The data show that EDA-containing fibronectin is essential for the fibrotic resolution of lung injury through TGF-beta activation and responsiveness, and suggest that EDA-containing fibronectin plays a critical role in tissue fibrogenesis.
Supercontinuum Generation in Optical Fibers (2010)

The optical fiber based supercontinuum source has recently become a significant scientific and commercial success, with applications ranging from frequency comb production to advanced medical imaging. This one-of-a-kind book explains the theory of fiber supercontinuum broadening, describes the diverse operational regimes and indicates principal areas of applications, making it a very important guide for researchers and graduate students. With contributions from major figures and groups who have pioneered research in this field, the book describes the historical development of the subject, provides a background to the associated nonlinear optical processes, treats the generation mechanisms from continuous wave to femtosecond pulse pump regimes and highlights the diverse applications. A full discussion of numerical methods and comprehensive computer code are also provided, enabling readers to confidently predict and model supercontinuum generation characteristics under realistic conditions.
Using Light-Induced Thermocleavage in a Roll-to-Roll Process for Polymer Solar Cells (2010)

We report on the use of intense visible light with a narrow spectral distribution matched to the region where the conjugated polymer material absorbs to selectively heat the active material and induce thermocleavage. We show a full roll-to-roll process, leading to complete large-area polymer solar cell modules using light-induced thermocleavage. The process employs full solution processing in air for all five layers in the device and does not employ indium-tin oxide or vacuum processing. The process steps were carefully analyzed using X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, attenuated total reflectance infrared, and transmission/reflection UV-vis techniques.
Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior (2006)

Os glicoesfingolipídios (GSLs) são importantes componentes da membrana celular, organizados em microdomínios, relacionados a receptores de membrana e comportamento anti-social da célula neoplásica como crescimento descontrolado, invasão e ocorrência de metástases. OBJETIVO: Como a expressão de GSLs no carcinoma espinocelular (CEC) é tema pouquíssimo estudado decidiu-se realizar estudo prospectivo visando avaliar a expressão de GSLs no CEC do trato aerodigestivo superior. MÉTODO: Coletou-se 33 amostras de CEC e mucosa normal e GSLs extraídos e purificados por cromatografia de fase reversa em coluna de C-18 e hidrólise alcalina em metanol. Os GSLs foram quantificados por densitometria das placas de cromatografia de alta resolução em camada delgada coradas com orcinol. RESULTADOS: Observou-se aumento significativo de GSLs no CEC (3,57µg/mg) em comparação à mucosa normal (1,92µg/mg), principalmente do monosialogangliosídeo (GM3), trihexosilceramida (CTH), dihexosilceramida (CDH), globosídeo (Gb4). A expressão de monohexosilceramida (CMH) foi semelhante no CEC e na mucosa normal. O aumento do GM3 no CEC foi demonstrado por métodos imunoquímicos empregando-se MAb DH2 (anti-GM3). Analisando-se os carboidratos do CMH por cromatografia gasosa acoplado a espectrômetro de massa constatou-se que a mucosa normal expressa glucosilceramida e o CEC glucosilceramida e galactosilceramida. CONCLUSÃO: O aumento de GSLs no tecido tumoral pode representar alterações dos microdomínios da membrana celular resultantes do processo de transformação maligna, responsáveis por uma maior interação célula-célula e célula-matriz aumentando seu potencial de infiltração e metástase, possibilitando o emprego dos GSLs e de MAbs no diagnóstico e no tratamento do CEC, a exemplo do que ocorre no melanoma.
E-16 CONTACT STRENGTH ANALYSIS FOR CERAMIC BALL IN BACKFLOW VALVE(Session: Contact strength/Mechanical) (2006)

Ceramics have the properties of high-stiffness, proof-corrosion, and light-weight superior to metal materials and so have been applied to a ball and a race in high performance ball bearing and etc. As a recent expansion of this application, a ceramics ball has been applied to the backflow valve, which is comprised in automotive fuel supply system. However, it must be considered sufficiently that ceramic balls can maintain a high confidence over long-term without being broken by cyclic contact loadings, which are generated between a ceramic ball and housing on switching a backflow valve. In this investigation, the stress analysis by FEM was conducted for clarifying failure mechanism due to cyclic contact stress. As results of analysis, the place of highest contact stress was seen directly underneath the contact region between a ball and housing. In ceramics of brittle material, the fracture occurs usually from a microscopic latent flaw in materials. Therefore, it was probabilistically clarified from a view-point of fracture mechanics that a latent internal microscopic flaw was a starting point of fracture.
CD4+ T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation (2000)

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express latent TGF-beta abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-beta in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent TGF-beta was activated in the inflammatory environment. In contrast, OVA-specific Th1 cells failed to inhibit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-beta-secreting Th cells was antigen-specific and was reversed by neutralization of TGF-beta. Our results demonstrate that T cells secreting TGF-beta in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation and suggest that TGF-beta-producing T cells play an important regulatory role in asthma.
RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker (2009)

The tumour suppressor gene RASSF1A is known to be frequently silenced by promoter hypermethylation in neuroblastoma tumours. Here we explored the possible prognostic significance of aberrant promoter hypermethylation of RASSF1A in serum DNA samples of patients with neuroblastoma as a surrogate marker for circulating tumour cells. We analysed the methylation status of the RASSF1A gene in matched tumour and pretreatment serum DNA obtained from 68 neuroblastoma patients. Hypermethylation of RASSF1A in tumour samples was found in 64 patients (94%). In contrast, serum methylation of RASSF1A was observed in 17 patients (25%). Serum methylation of RASSF1A was found to be statistically associated with age > or =12 months at diagnosis (P=0.002), stage 4 (P<0.001) and MYCN amplification (P<0.001). The influence of serum RASSF1A methylation on prognosis was found to be comparable with that of the currently most reliable marker, MYCN amplification on univariate analysis (hazard ratio, 9.2; 95% confidence interval (CI), 2.8-30.1; P<0.001). In multivariate analysis of survival, methylation of RASSF1A in serum had a hazard ratio of 2.4 (95% CI, 0.6-9.2), although this association did not reach statistical significance (P=0.194). These findings show that the methylation status of RASSF1A in the serum of patients with neuroblastoma has the potential to become a prognostic predictor of outcome.
CONTINUOUS ARTERIOVENOUS HEMODIAFILTRATION IN THE ACUTE TREATMENT OF HYPERAMMONAEMIA DUE TO ORNITHINE TRANSCARBAMYLASE DEFICIENCY (2000)

Continuous renal replacement therapy including CAVH, CAVHD, and CAVHDF may be the alternative techniques for acute management of hyperammonemia in inborn error of metabolism when dialysis machine is not available. Our data suggests CAVHDF provides the best ammonia clearance.
Metatranscriptomic analysis of autonomously collected and preserved marine bacterioplankton (2011)

Planktonic microbial activity and community structure is dynamic, and can change dramatically on time scales of hours to days. Yet for logistical reasons, this temporal scale is typically under-sampled in the marine environment. In order to facilitate higher-resolution, long-term observation of microbial diversity and activity, we developed a protocol for automated collection and fixation of marine microbes using the Environmental Sample Processor (ESP) platform. The protocol applies a preservative (RNALater) to cells collected on filters, for long-term storage and preservation of total cellular RNA. Microbial samples preserved using this protocol yielded high-quality RNA after 30 days of storage at room temperature, or onboard the ESP at in situ temperatures. Pyrosequencing of complementary DNA libraries generated from ESP-collected and preserved samples yielded transcript abundance profiles nearly indistinguishable from those derived from conventionally treated replicate samples. To demonstrate the utility of the method, we used a moored ESP to remotely and autonomously collect Monterey Bay seawater for metatranscriptomic analysis. Community RNA was extracted and pyrosequenced from samples collected at four time points over the course of a single day. In all four samples, the oxygenic photoautotrophs were predominantly eukaryotic, while the bacterial community was dominated by Polaribacter-like Flavobacteria and a Rhodobacterales bacterium sharing high similarity with Rhodobacterales sp. HTCC2255. However, each time point was associated with distinct species abundance and gene transcript profiles. These laboratory and field tests confirmed that autonomous collection and preservation is a feasible and useful approach for characterizing the expressed genes and environmental responses of marine microbial communities.