gebhart/patrepeval huggingface dataset:
Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization. (1995)

Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses were 5 times more common than gains and most often involved 8p (32%), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus 0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.
Essential fatty acid deficiency in patients with severe fat (1997)

Essential fatty acid deficiency is commonly de- scribed in patients receiving parenteral nutrition, but the occur- rence in patients with severe fat malabsonption not receiving panenteral nutrition is uncertain. One hundred twelve patients were grouped according to their degree of fat malabsonption: group 1, 50% (ii = 15). Fecal fat was measured by the method of Van de Kamer the last 2 of 5 d of a 75-g fat diet. Serum fatty acids in the phospholipid fraction were measured by gas-liquid chromatography after separation by thin-layer chroma- tography and expressed as a percentage of total fatty acids. The concentration of linoleic acid in groups 1, 2, 3, and 4 was 2 1.7%, 19.4%, 16.4%, and 13.4% respectively (P 25-50% of dietary fat intake and not treated with parenteral nutrition have biochemical signs of essential fatty acid deficiency. The clinical effect of these changes are yet to be elucidated. Am J C/in Nutr 1997:65:837-43.
Caracterização de isolados de Acidovorax avenae subsp. citrulli (2007)

Foram caracterizados 41 isolados de Acidovorax avenae subsp. citrulli com base em aspectos fisiológicos e bioquímicos. Todos os isolados induziram sintomas típicos da mancha-aquosa em plântulas, plantas e frutos de meloeiro (Cucumis melo) e melancieira (Citrullus lanatus). Pelo teste de agrupamento de Scott-Knott (P = 0,05) os isolados foram separados quanto ao índice de doença em 5 e 7 grupos, respectivamente para plântulas de meloeiro e melancieira, e em 2 grupos para plantas das duas hospedeiras. Em frutos, os isolados foram separados em 3 e 10 grupos para a variável diâmetro da lesão externa e 2 e 9 grupos para profundidade da lesão, respectivamente para melão e melancia. Todos os isolados induziram reação de hipersensibilidade em fumo (Nicotiana tabacum); utilizaram os compostos asparagina, L-leucina e DL-ácido lático; produziram enzimas lipolíticas e o fitohormônio ácido indol acético; foram sensíveis a oxicloreto de cobre (120 µg mL-1), óxido cuproso (120 µg mL-1), hidróxido de cobre (138,2 µg mL-1), sulfato de estreptomicina (25 µg mL-1) e Agrimaicin 500 (428 µg mL-1); e resistentes a kasugamicina (87 µg mL-1), agrimicina (200 µg mL-1), eritromicina (15 µg), gentamicina (10 µg), amoxicilina (10 µg), neomicina (30 µg), estreptomicina (10 µg), norfloxacina (10 µg) e rifampicina (5 µg). Nenhum isolado apresentou atividade pectinolítica, amilolítica, celulolítica e proteolítica ou produção do polissacarídeo levana e da toxina siringomicina. Foi constatada variabilidade entre os 41 isolados de A. avenae subsp. citrulli quanto à sensibilidade à tetraciclina (30 µg), sendo 41,5% resistentes, 46,3% moderadamente sensíveis e 12,2% altamente sensíveis.
Cultures of Human Adipose Precursor Cells (2003)

Recently, there has been rapidly growing interest in cell culture models that allow the study of the adipose differentiation process in vitro, as well as the long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Although valuable clonal preadipocyte cell lines of rodent origin have been available for more than 20 yr, it became more and more obvious from subsequent studies that substantial differences exist in the developmental stage and regulation of differentiation, as well as in specific adipocyte functions, between rodent and human AT (, , ). This knowledge makes it necessary to use human cell culture models, if specific questions concerning human AT metabolism and the mechanisms that may lead to either hypertrophic or hyperplastic growth in humans are investigated. Another aspect that is currently attracting considerable attention is the secretory function of adipocyte precursors and fat cells. Numerous factors are released from these cells, and maintain an intense crosstalk with distant organs, or act at the local level ().
In vitro and in vivo release of gentamicin from biodegradable discs (2006)

Osteomyelitis is an infection of the bone and successful treatment involves the removal of the affected bone and the tissue by a surgical procedure following prolonged systemic and local antibiotic therapy for 4 to 6 weeks. The current local treatment is done by poly methyl methacrylate (PMMA) beads loaded with gentamicin and PMMA, being nondegradable, is to be removed by a second surgical procedure. The current study aims to develop a biodegradable composition that gives sustained release and hence reducing the need for a second surgery. Gentamicin-loaded discs were produced by compressing microparticle-gentamicin mixture obtained by spray drying a mixture of gentamicin in a solution of a biodegradable polymer. Different copolymers of poly (DL-lactic-co-glycolic acid) (PLGA) were used to study the effect of copolymer ratio and the hydrophilic-hydrophobic nature of the polymer. Theoretical drug loading up to 25% were studied and it was observed that 10% drug loading was optimum for gentamicin to be used as solid in spray drying. The results showed that about 60% of the drug is released in about 5 to 6 days and the remaining drug is released in about 30 days in total. An in vivo study was carried on rabbit femur and the local area and systemic concentration of gentamicin was monitored. It was observed that the local area concentration of gentamicin was above minimum inhibitory concentration for more than 20 days and this was also validated by computer simulations.
Permeabilising effects of sub-inhibitory concentrations of microcystin on the growth ofEscherichia coli (2003)

Microcystin, a cyanotoxin produced by Microcystis aeruginosa, lacks potent antibacterial activity. When tested in combination, in vitro, inhibitory values for a range of hydrophobic antibiotics were significantly reduced in the presence of at least 1/20 x the minimum inhibitory concentration of microcystin. The degree of inhibition was equivalent to that of a well-characterised permeabilizing agent, polymyxin B nonapeptide. The permeabilizing ability of sub-inhibitory concentrations of microcystin to affect the envelope of Escherichia coli was demonstrated by a rapid and sustained reduction in absorbance values of lysozyme-treated cells and by enhanced uptake of crystal violet in microcystin-treated cultures. Direct effects of appropriate concentrations of microcystin on the integrity of bacterial outer and inner membranes were measured by release of specific enzyme markers. Although the exact mechanism for permeabilizing E. coli with microcystin has not been elucidated, the effects were consistent with permeability changes to the enterobacterial outer membrane caused by polymyxin B nonapeptide.
Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins (1998)

Alcohol based cosolvents, such as trifluoroethanol (TFE) have been used for many decades to denature proteins and to stabilize structures in peptides. Nuclear magnetic resonance spectroscopy and site directed mutagenesis have recently made it possible to characterize the effects of TFE and of other alcohols on polypeptide structure and dynamics at high resolution. This review examines such studies, particularly of hen lysozyme and beta-lactoglobulin. It presents an overview of what has been learnt about conformational preferences of the polypeptide chain, the interactions that stabilize structures and the nature of the denatured states. The effect of TFE on transition states and on the pathways of protein folding and unfolding are also reviewed. Despite considerable progress there is as yet no single mechanism that accounts for all of the effects TFE and related cosolvents have on polypeptide conformation. However, a number of critical questions are beginning to be answered. Studies with alcohols such as TFE, and 'cosolvent engineering' in general, have become valuable tools for probing biomolecular structure, function and dynamics.
Handling heterogeneity in RosettaNet messages (2007)

We present a semantic B2B gateway based on the WSMX semantic Service-Oriented Architecture to tackle heterogeneities in RosettaNet messages. We develop a rich RosettaNet ontology and use the axiomatised knowledge and rules to resolve data heterogeneities and to unify unit conversions. We use adaptive executable choreography definitions to easily integrate new sellers into existing RosettaNet collaborations.
Rheology of colloidal suspensions: Case of lubricating greases (1994)

Lubricating greases are two-phase colloidal suspensions consisting essentially of a mineral oil and a metal-soap based thickener forming a three-dimensional gelling network. This study examines the rheology of two greases, based on lithium soap and calcium complexes, under steady, transient and dynamic flow conditions, with homogeneous shear being applied in a cone-plate geometry. Controlled speed and controlled torque rheometers were used in this study. Various precautions need to be taken in order to obtain reliable results. These include checking and eliminating slip at the walls and fracture, correct choice of apparatus, and suitable measurement procedures. It is shown that discrepancies may arise as a result of choosing the wrong test procedures. The lithium grease is characterized by a yield stress and shear-thinning behavior, whereas the calcium complex has a minimum in the flow curve, for which controlled torque rheometer measurements are not the most suitable. Original test procedures are adopted for studying viscoelasticity and thixotropy, the importance of which depends on the type of constituents involved.
Fusion as a mediator of cytolysis in mixtures of uninfected CD4+ lymphocytes and cells infected by human immunodeficiency virus. (1987)

We describe an unusual type of cytopathology in which uninfected CD4+ (helper/inducer) cells (cells expressing the human leukocyte antigen CD4) interact with cells persistently infected with the human immunodeficiency virus (HIV). Prior antigenic stimulation was not required, since CD4+ cells taken either from healthy persons without anti-HIV antibodies or from individuals with anti-HIV antibodies were capable of inducing cytolysis. Neither CD8+ (suppressor/cytotoxic) nor CD16+ (natural killer) cells mediated the reaction. Light microscopic and autoradiographic studies revealed that, prior to cytolysis, multinucleated giant cells were formed from fusions between HIV-infected cells and large numbers of uninfected CD4+ lymphocytes. These data may explain the paradox that exists in vivo in which a dramatic depletion of CD4+ lymphocytes occurs in the presence of a small number of HIV-infected CD4+ cells. These new insights into the pathogenesis of acquired immunodeficiency syndrome (AIDS) may lead to future therapeutic strategies.
X-ray Crystal Structure of 28-O-Methylrapamycin complexed with FKBP12: Is the Cyclohexyl Moiety Part of the Effector Domain of Rapamycin? (2012)

The X-ray crystal structure of 28-O-methylrapamycin 2 bound to FKBP12 is described. This rapamycin analogue binds to FKBP12 with an affinity comparable to that of rapamycin, but its immunosupressiv...
Clinical value of bisphosphonates in cancer therapy. (2007)

The therapeutic opportunities for an improved management of malignant bone disease are currently extensively studied. The conventional management of symptomatic bone lesions in patients with advanced cancer involves various combinations of local and systemic standard anticancer therapies and the symptomatic treatment of skeletal complications. In recent years, bisphosphonates have demonstrated high efficacy to avoid skeletal complications from metastatic bone lesions and to prevent cancer treatment-induced bone loss. Especially in the treatment of patients with bone metastases, secondary to breast cancer, a widespread use of bisphosphonates has been established. With the development of highly potent new-generation bisphosphonates, such as zoledronate, the therapeutic opportunities for bisphosphonates are going to expand. Several current studies have investigated the benefit of zoledronate therapy for bone metastases from a variety of tumor types, including prostate cancer, lung and renal cell cancer and multiple myeloma. Furthermore, bisphosphonates have been shown to significantly reduce antineoplastic therapy-induced bone loss. According to recently published data, it is suggested that bisphosphonates not only play a role in the inhibition of osteoclast-mediated bone resorption, but also have antitumor effects inhibiting tumor cell proliferation, adhesion and invasion, as well as angiogenesis and induction of apoptosis. Further preclinical and clinical investigations are necessary to elucidate the role of bisphosphonates, and large randomized clinical trials should be conducted to confirm the clinical value of bisphosphonates for the prevention of relapse, as well as for the maintainance of net bone density, e.g. during aromatase inhibitor therapy.
Steady‐State Continuous‐Flow Purification by Electrophoresis (2013)

Bubble and sweep: Free-flow electrophoresis (FFE) could allow continuous-flow purification of products from continuous-flow microsynthesis. However, gas bubbles distort the separation. An open-electrolyte FFE system avoids this problem. Electrodes placed in chimneys open to the atmosphere mean bubbles are vented directly from the system and cannot enter the separation channel (see picture).
A New Method for Intense Staining of Myelin (1998)

We describe a new method for intense staining of myelin. The stain involves immersing frozen or vibratome sections of 4% normal horse serum. A DAB reaction is then carried out, which results in the deposition of reaction product in myelin sheaths. On intensification of this reaction product using the silver enhancement technique described by Görcs, myelin stains an intense black color, making the preparations suitable for photography. The stain is especially useful for determining the distribution of myelinated fibers in gray matter.
Role of protein subunits in Proteus rettgeri penicillin G acylase (1985)

Penicillin G acylase from Proteus rettgeri is an 80,000- to 90,000-dalton enzyme composed of two nonidentical subunits. Both subunits were required for enzymatic activity. The 65,000-dalton beta subunit contained a phenylmethylsulfonyl fluoride-sensitive residue required for enzymatic activity, and the 24,500-dalton alpha subunit contained the domain that imparts specificity for the penicillin side chain.
Structure-Based Design of Potent and Selective 2-(Quinazolin-2-yl)phenol Inhibitors of Checkpoint Kinase 2 (2010)

Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl)phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2-(quinazolin-2-yl)phenol 46 (IC(50) 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of kinases and with promising in vitro ADMET properties. Off-target activity at hERG ion channels shown by the core scaffold was successfully reduced by the addition of peripheral polar substitution. In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533).
The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer (2014)

PD-1 pathway inhibition represents a new frontier in cancer immunotherapy, which shows clear evidence of activity in various tumor types including NSCLC and melanoma. Ongoing and upcoming trials will examine optimal combinations of these agents, which should further define their role across tumor types. Current limitations include the absence of a reliable companion diagnostic to predict likely responders, as well as lack of data in early-stage cancer when treatment has the potential to increase cure rates.
Dilated Cardiomyopathy: Computer-Assisted Analysis of Endomyocardial Biopsy Protein Patterns by Two-Dimensional Gel Electrophoresis (1994)

In order to identify disease-associated alterations in the myocardial protein patterns in dilated cardiomyopathy, we used 2-dimensional gel electrophoresis to analyse the proteins of endomyocardial biopsies from patients and controls. Proteins (150 micrograms) from biopsies (1-3 mg wet weight) were first separated by isoelectric focusing, then applied to large 2-dimensional gels. A computer-assisted system (PDQUEST) was used for spot detection, quantification and comparison of 2-dimensional protein patterns. From a single endomyocardial biopsy about 1000 different protein species were resolved. The spot pattern was influenced by the concentration of protein during sample preparation, by the amount of protein loaded onto the gels and by the development time of silver staining. Variances of spot position in the first and second dimension and in the long diagonals were less than 5%. Coefficients of variance for the spot quantities in 8 gels were 16 +/- 8%. Contaminating blood proteins could be identified in the biopsy patterns. Computer-assisted comparison between cardiomyopathy (n = 5) and controls (n = 5) over the whole gel revealed that 55 protein spots were increased 100%, 27 protein spots decreased 100%. Four proteins showed significant quantitative differences between the cardiomyopathic hearts and controls. Fourteen proteins were identified by amino acid analysis or microsequencing. An isoelectric point and molecular mass grid was laid over the whole gel based on these identified protein species, resulting in approximate isoelectric point values and molecular masses for all other protein species. Thus, myocardial 2-dimensional protein patterns obtained from endomyocardial biopsies can be used for the characterization of cardiac diseases.
Rhythmic Brushstrokes Distinguish van Gogh from His Contemporaries: Findings via Automated Brushstroke Extraction (2011)

Art historians have long observed the highly characteristic brushstroke styles of Vincent van Gogh and have relied on discerning these styles for authenticating and dating his works. In our work, we compared van Gogh with his contemporaries by statistically analyzing a massive set of automatically extracted brushstrokes. A novel extraction method is developed by exploiting an integration of edge detection and clustering-based segmentation. Evidence substantiates that van Gogh's brushstrokes are strongly rhythmic. That is, regularly shaped brushstrokes are tightly arranged, creating a repetitive and patterned impression. We also found that the traits that distinguish van Gogh's paintings in different time periods of his development are all different from those distinguishing van Gogh from his peers. This study confirms that the combined brushwork features identified as special to van Gogh are consistently held throughout his French periods of production (1886-1890).
Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation. (1988)

The genes for platelet-derived growth factor (PDGF) A chain, B chain/c-sis, and the PDGF receptor are expressed in human malignant glioma cell lines. In the present investigation we have studied the expression of these genes in biopsy specimens from human glioblastomas. Hyperplasia of the vascular endothelium is a prominent characteristic of human glioblastoma multiforme and simian sarcoma virus-induced gliomas in primates. RNA transfer blot analysis of biopsies from glioblastoma multiforme showed transcripts for PDGF A and B chains and the PDGF receptor. Tissue sections from this tumor examined by in situ hybridization techniques revealed that the proliferating vascular endothelial cells contained large quantities of mRNA for PDGF B chain/c-sis and its receptor and, to a lesser extent, for PDGF A chain. In contrast, the tumor cells expressed more mRNA for PDGF A chain than for PDGF B chain and PDGF receptor. The latter two were also expressed at higher levels in glioma cells than in glial cells of nontumorous human brain tissue. Thus, an autocrine stimulation by the PDGF B chain/c-sis product via its receptor, evoked by interaction with surrounding glioma cells, could be the mechanism behind the pathological proliferation of endothelial cells characteristically found in this type of malignancy.
Multiple Roles for the Receptor Tyrosine Kinase Axl in Tumor Formation (2005)

A focus of contemporary cancer therapeutic development is the targeting of both the transformed cell and the supporting cellular microenvironment. Cell migration is a fundamental cellular behavior required for the complex interplay between multiple cell types necessary for tumor development. We therefore developed a novel retroviral-based screening technology in primary human endothelial cells to discover genes that control cell migration. We identified the receptor tyrosine kinase Axl as a novel regulator of endothelial cell haptotactic migration towards the matrix factor vitronectin. Using small interfering RNA-mediated silencing and overexpression of wild-type or mutated receptor proteins, we show that Axl is a key regulator of multiple angiogenic behaviors including endothelial cell migration, proliferation, and tube formation in vitro. Moreover, using sustained, retrovirally delivered short hairpin RNA (shRNA) Axl knockdown, we show that Axl is necessary for in vivo angiogenesis in a mouse model. Furthermore, we show that Axl is also required for human breast carcinoma cells to form a tumor in vivo. These findings indicate that Axl regulates processes vital for both neovascularization and tumorigenesis. Disruption of Axl signaling using a small-molecule inhibitor will hence simultaneously affect both the tumor and stromal cell compartments and thus represents a unique approach for cancer therapeutic development.
Reduction of Cisplatin-Induced Emesis by a Selective Neurokinin-1–Receptor Antagonist (1999)

The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin. Moreover, combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis.