gebhart/patrepeval huggingface dataset:
In vitro biocompatibility of polyetheretherketone and polysulfone composites (1990)

Short carbon fiber reinforced composites could potentially replace some of the metal alloys used in orthopedic implants. In particular, polysulfone and, more recently, polyetheretherketone have been considered as the matrix material for carbon fiber reinforced composite implant materials. ASTM standards F813 and F619 for direct contact cell culture evaluation and extraction were employed to determine the in vitro biocompatibility of a carbon fiber composite of polyetheretherketone, PEEK, in comparison to a carbon fiber reinforced polysulfone composite. The cell cultures were assessed qualitatively by microscopy and quantitatively using an enzyme assay to determine cytotoxicity. Overall, the cellular response to the PEEK and polysulfone composites were negligible indicating that further in vivo studies with these materials are appropriate.
Blood cortisol and dehydroepiandrosterone sulphate (DHEAS) levels and CD4 T cell counts in HIV infection. (1997)

Whether low DHEAS levels might contribute to some of the pathophysiologic features and/or symptoms seen in HIV infection needs to be investigated.
ESSENTIAL FATTY ACIDS AND HUMAN DISEASE (1958)

Journal Article ESSENTIAL FATTY ACIDS AND HUMAN DISEASE Get access A. T. JAMES, Ph.D., A. T. JAMES, Ph.D. National Institute for Medical Research Mill HillLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. LOVELOCK, Ph.D. J. E. LOVELOCK, Ph.D. National Institute for Medical Research Mill HillLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 14, Issue 3, September 1958, Pages 262–266, https://doi.org/10.1093/oxfordjournals.bmb.a069694 Published: 01 September 1958
Comparison of G-Protein Coupled Receptor Desensitization-Related &#946;- Arrestin Redistribution Using Confocal and Non-Confocal Imaging (2005)

High Content Screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modelling systems. In this work, we compared a confocal and a non-confocal cellular HCS system, the IN Cell Analyzers(1) 3,000 and 1,000, respectively. As a cellular model system we used the Transfluor technology in the 384-well microtiter plate (MTP) format. The Transfluor HCS assay for G-protein coupled receptor (GPCR) activation is based on the recruitment of a green fluorescent protein-labelled arrestin (ArrGFP) from the cytosol to the plasma membrane. We investigated two GPCRs, the wild-type (wt) beta2 adrenergic receptor (beta2AR) and the beta2AR-enhanced (E), a C-terminally mutated receptor with a higher affinity to arrestin. Upon agonist stimulation, the beta2AR-wt induced the redistribution of ArrGFP to coated pits, the beta2AR-E maintained the interaction with ArrGFP down to the formation of endocytic vesicles. Our findings reveal that the assay is feasible on both instruments, with sufficiently robust Z' statistics. Improved Z' statistics, though, are achieved with the confocal system, particularly in case of weak signals. Moreover, throughput is dramatically higher for the IN Cell Analyzer 3,000. We conclude that, depending on the needs for throughput and assay biology, either instrument may fulfil a successful role in the drug discovery process. Confocal optics, however, provide a better basis for the detection of smaller subcellular structures with lower fluorescence intensity.
Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by instrastriatal injection of 6-hydroxydopamine (1995)

Animal models with partial lesions of the dopaminergic nigrostriatal pathway may be useful for developing neuroprotective and neurotrophic therapies for Parkinson's disease. To develop such a model, different doses of 6-hydroxydopamine (0.0, 0.625, 1.25, 2.5 and 5.0 micrograms/microliters in 3.5 microliters of saline) were unilaterally injected into the striatum of rats. Animals that received 1.25 to 5.0 micrograms/microliters 6-hydroxydopamine displayed dose-dependent amphetamine and apomorphine-induced circling. 6-Hydroxydopamine also caused dose-dependent reductions in [3H]mazindol-labeled dopamine uptake sites in the lesioned striatum and ipsilateral substantia nigra pars compacta (up to 93% versus contralateral binding), with smaller losses in the nucleus accumbens, olfactory tubercle and ventral tegmental area. In the substantia nigra pars compacta and the ventral tegmental area, the number of Nissl-stained neurons decreases in parallel with the reduction in [3H]mazindol binding. The reduction in [3H]mazindol binding in the striatum and the nucleus accumbens, and the reduction in [3H]mazindol binding and in the number of Nissl-stained neurons in the substantia nigra pars compacta and the ventral tegmental area is stable for up to 12 weeks after the lesion. Macroscopically, forebrain coronal sections showed normal morphology, except for rats receiving 5.0 micrograms/microliters 6-hydroxydopamine in which striatal cross-sectional area was reduced, suggesting that this high dose non-specifically damages intrinsic striatal neurons. Nissl-stained sections revealed an area of neuronal loss and intense gliosis centered around the needle track, which increased in size with the dose of neurotoxin. Striatal [3H]sulpiride binding was increased by 2.5 micrograms/microliters and 5.0 micrograms/microliters 6-hydroxydopamine, suggesting up-regulation of dopamine D2 receptors. Striatal binding of [3H]CGS 21680-labeled adenosine A2a receptors, but not of [3H]SCH 23390-labeled dopamine D1 receptors, was reduced at the highest dose, suggesting preservation of the striatal intrinsic neurons with the lower doses. This study indicates that intrastriatal injection of different doses of 6-hydroxydopamine can be used to cause increasing amounts of dopamine denervation, which could model Parkinson's disease of varying degrees of severity. Injecting 3.5 microliters of 2.5 micrograms/microliters 6-hydroxydopamine appears to be particularly useful as a general model of early Parkinson's disease, since it induces a lesion characterized by robust drug-induced rotation, changes in binding consistent with approximately 70% dopamine denervation, approximately 19% dopamine D22 receptor up-regulation, negligible intrinsic striatal damage and stability for at least 12 weeks. This study outlines a technique for inducing partial lesions of the nigrostriatal dopamine pathway in rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Down regulation in B lymphocytes: low dose signals (1977)

Picogram quantities of dinitrophenylated (DNP) dextran, a thymus-independent antigen or lipopolysaccharide, a B cell mitogen, signal down B lymphocytes to unresponsiveness. Down signals were detected by a decision test in which signaled lymphocytes were allowed one hour to react to an immunogenic pulse of DNP-dextran. Depletion of T cells or macrophages did not interfere with the generation of down signals. The signaling can proceed entirely at 4 degrees C and it its negative effect is transitory. Down signals which could be detected after 15 min at 37 degrees C were reversed by 60 min. It is suggested that down regulation by low dose antigenic signals provides a means of distinguishing background noise from true antigenic stimuli.
Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication‐naïve adolescents with depression compared to controls (2009)

This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.
Thrombolysis of occluded infrainguinal bypass grafts. (1997)

From January 1993 to December 1995, intraarterial catheter guided urokinase infusion was used as an initial approach in the management of 29 episodes of infrainguinal graft thrombosis (12 venous and 17 prosthetic grafts) in 27 patients. The infusion catheter was embedded inside the occluding clot which was infiltrated by 225.000 U urokinase from distal to proximal. Local low-dose urokinase (1.000 U/kg/hr) was continued for a mean of 39 hours. By this regimen, prompt relief of ischaemia was achieved in 69% (20/29) of cases. Complete recanalization was obtained in 79% of cases. In six cases, the graft remained totally (n = 3) or partially (n = 3) occluded. Two of these patients benefited from secondary surgery, two improved clinically by conservative treatment, and two required amputation. In the 23 successful cases, thrombolysis unmasked an underlying flow-limiting stenosis in 83% (19/23), that was subsequently corrected by percutaneous balloon angioplasty (n = 15), by surgery (n = 3), or by a combination of both (n = 4). One early rethrombosis resulted in an amputation. The immediate limb-salvage rate was 89% (26/29). Surgical intervention was avoided in 17 cases (58%). The main hospital stay was 13 days. The short-term follow-up (mean of 17 months) reveals a high early rethrombosis rate (8/23 or 35%) within one year. Four of these repeated graft failures evolved to amputation. At one year, the overall limb salvage rate dropped to 79%. Thrombolytic management of infrainguinal occluded bypass grafts gives excellent initial technical results (79%), minimizing the need for major surgical revision. It is however characterized by a high procedure-related morbidity (21%). These immediate favourable results are not longstanding. Diffuse graft disease, limited outflow and high recurrence rate of anastomotic stenoses after balloon angioplasty explain poor long-term results after thrombolysis of failed grafts.
Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer (2000)

Angiogenesis is esential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and is an important component of the angiogenic stimulus in a range of human neoplasias. In addition to its mitogenic activities, VEGF has also been found to stimulate migration in macrophages via the flt-1 VEGF receptor. It has previously been shown that increased focal tumour macrophage infiltration is associated with increased angiogenesis and worsened relapse-free and overall survival in breast cancer. Macrophages are able to stimulate angiogenesis by their production of a range of factors including VEGF, tumour necrosis factor-alpha (TNF-alpha), and thymidine phosphorylase (TP). Thus, in breast cancer, VEGF could have a dual role in the regulation of angiogenesis, by direct mitogenic stimulation of endothelial cells, and also indirectly by attracting macrophages into avascular tumours. The purpose of this study was to localize VEGF protein in a series of 96 consecutive primary breast carcinomas and to determine its relationship to focal macrophage infiltration (macrophage index). These two variables were also compared with the pathological features of the tumours, as well as oestrogen receptor (ER), epidermal growth factor receptor (EGFR), microvessel density, macrophage index, and survival. An inverse relationship (p=0.0006) was noted between VEGF and EGFR, with high VEGF expression correlating with low EGFR levels. In the EGFR-negative group of cases (n=56), positive associations were observed between VEGF expression and macrophage index (p=0.005), ER (p=0.05), p53 (p=0. 006), tumour grade (p=0.02), and tumour necrosis (p=0.03). Macrophage counts were higher in EGFR-positive tumours (p=0.0006) and no associations were found between VEGF expression and increased microvessel density. These results show that in breast cancers there are two types of macrophage infiltrates, one associated with the presence of EGFR and low VEGF expression in tumours and the other with high VEGF expression in EGFR-negative tumours. VEGF expression may be an important factor in the recruitment of tumour-associated macrophages into breast carcinomas and may thus have an additional, indirect, pathway of angiogenic stimulation in this type of tumour.
A fully human chimeric antigen receptor with potent activity against cancer cells but reduced risk for off-tumor toxicity (2015)

// De-Gang Song 1 , Qunrui Ye 1 , Mathilde Poussin 1 , Lin Liu 1 , Mariangela Figini 2 , Daniel J. Powell Jr 1, 3 1 Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 2 Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 3 Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Correspondence to: Daniel J. Powell Jr, e-mail: poda@mail.med.upenn.edu Keywords: folate receptor alpha, chimeric antigen receptor, adoptive immunotherapy, ovarian cancer, T cells Received: February 13, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: June 08, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: June 19, 2015 ABSTRACT Chimeric antigen receptors (CARs) can redirect T cells against antigen-expressing tumors in an HLA-independent manner. To date, various CARs have been constructed using mouse single chain antibody variable fragments (scFvs) of high affinity that are immunogenic in humans and have the potential to mediate &ldquo;on-target&rdquo; toxicity. Here, we developed and evaluated a fully human CAR comprised of the human C4 folate receptor-alpha (&alpha;FR)-specific scFv coupled to intracellular T cell signaling domains. Human T cells transduced to express the C4 CAR specifically secreted proinflammatory cytokine and exerted cytolytic functions when cultured with &alpha;FR-expressing tumors in vitro . Adoptive transfer of C4 CAR T cells mediated the regression of large, established human ovarian cancer in a xenogeneic mouse model. Relative to a murine MOv19 scFv-based &alpha;FR CAR, C4 CAR T cells mediated comparable cytotoxic tumor activity in vitro and in vivo but had lower affinity for &alpha;FR protein and exhibited reduced recognition of normal cells expressing low levels of &alpha;FR. Thus, T cells expressing a fully human CAR of intermediate affinity can efficiently kill antigen-expressing tumors in vitro and in vivo and may overcome issues of transgene immunogenicity and &ldquo;on-target off-tumor&rdquo; toxicity that plague trials utilizing CARs containing mouse-derived, high affinity scFvs.
Stability of Vitamins C and E in Topical Microemulsions for Combined Antioxidant Therapy (2007)

An interesting strategy for protecting skin from excessive exposure to free radicals is to support the skin endogenous antioxidant system. As the balance between different skin antioxidants is very important, a combined therapy using at least two antioxidants is desirable. In the present work, o/w, w/o, and gel-like microemulsions (ME), all composed of the same ingredients, were selected as carrier systems for dermal delivery of vitamins C and E. Gel-like ME was found to offer the best protection for both vitamins, although other ME also significantly increased their stability compared with that solution. In the presence of vitamin C no decrease in vitamin E content occurred. To obtain ME appropriate for dermal use, their viscosity was increased by adding thickening agents. On the basis of visual examination of viscosity and physical stability of thickened systems, several thickeners were selected. The addition of thickener significantly increased the viscosity of ME and changed the behavior of systems from ideal Newtonian to thixotropic. Finally, the stability of both vitamins was examined as a function of thickening agent and of the location of vitamins in the ME. The addition of thickeners changed the stability of at least one vitamin, but the systems generally still protected vitamins better than solutions. It is likely that the changes in internal organization of ME resulting from the addition of thickener, confirmed by thermal analysis and changes in solubility of oxygen in the outer phase, were the most important factors that influenced the stability of vitamins in thickened systems.
RNA silencing platforms in plants (2005)

Since the discovery of RNAi, its mechanism in plants and animals has been intensively studied, widely exploited as a research tool, and used for a number of potential commercial applications. In this article, we discuss the platforms for delivering RNAi in plants. We provide a brief background to these platforms and concentrate on discussing the more recent advances, comparing the RNAi technologies used in plants with those used in animals, and trying to predict the ways in which RNAi technologies may further develop.
A segment-based wordspotter using phonetic filler models (2002)

A common approach to wordspotting is to augment the keyword models with "filler" models to account for nonkeyword intervals. An alternative approach is to use a large vocabulary continuous speech recognition system (LVCSR) to produce a word string, and then search for the keywords in that string. While the latter approach typically yields higher performance, it requires costly computation and extensive training data. We develop several segment-based wordspotters in an effort to achieve performance comparable to that of the LVCSR spotter, but with only a fraction of the vocabulary. We investigate several methods to model the background, ranging from a few general models to refined phone representations. The task is to detect sixty-one keywords from continuous speech in the ATIS domain. The best performance we achieve is 91.4% figure of merit for the LVCSR spotter and 86.7% for a spotter using 57 phone-based filler models.
Macrophage colony-stimulating factor regulates both activities of neutral and acidic cholesteryl ester hydrolases in human monocyte-derived macrophages. (1993)

Macrophage colony-stimulating factor (M-CSF) regulates cholesterol metabolism in vivo and in vitro. We studied the effects of M-CSF on enzyme activities of acidic cholesteryl ester (CE) hydrolase, neutral CE hydrolase, and acyl-coenzyme A:cholesterol acyltransferase (ACAT), all of which are involved in cellular cholesterol metabolism in macrophages. During the differentiation of monocytes to macrophages, these enzyme activities were induced and further enhanced in response to M-CSF. M-CSF (100 ng/ml) enhanced acidic and neutral CE hydrolase and ACAT activities by 3.2-, 4-, and 2.3-fold, respectively, in the presence of acetyl LDL. The presence of acetyl LDL influenced these enzyme activities. ACAT and acidic CE hydrolase activities were increased and neutral CE hydrolase activity was decreased, indicating that these enzymes are regulated by intracellular cholesterol enrichment. M-CSF increased the ratios of acidic CE hydrolase to ACAT activity and of neutral CE hydrolase to ACAT activity. The results suggest that M-CSF enhances net hydrolysis of CE by stimulating the two CE hydrolases to a greater extent than ACAT, and M-CSF may reduce the rate of atherogenesis.
Method for the isolation of highly purified Salmonella flagellins (1985)

Ten different Salmonella serotypes were grown in a chemically defined medium supplemented with 0.01% yeast extract. After sedimentation of the cells by centrifugation, flagella were detached by exposure to pH 2 for 30 min at room temperature. The flagellaless cells were removed by centrifugation, and the flagellin in the supernatant was further purified by high-speed centrifugation, ammonium sulfate precipitation, and dialysis in 50,000-molecular-weight-cutoff tubing. The 10 flagellin preparations were of a high degree of purity, as demonstrated by electron microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and measurement of salmonella H and O agglutination titers of antisera raised in rabbits with the flagellin preparations as immunogens.
Induction of Cytosolic Phospholipase A2 by Oncogenic Ras in Human Non-small Cell Lung Cancer (1997)

Mutations in Ras family members that confer oncogenic potential are frequently observed in specific human cancers. We report that human non-small cell lung cancer (NSCLC) lines that harbor oncogenic mutations in Ki-Ras (H460, A549, H2122) synthesized high levels of prostaglandin E2 (PGE2) compared with NSCLC lacking Ras mutations or non-transformed lung epithelial cells (BEAS-2B). This increased PGE2 production was mediated by constitutively high expression of 85-kDa cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2). The increased expression of cPLA2 protein was mediated through elevated mRNA levels and activation of the cPLA2 promoter. Induction of cPLA2 promoter activity was blocked by expression of dominant-negative forms of Ras. Inhibition of Ras by the farnesyltransferase inhibitor BZA-5B inhibited prostaglandin synthesis in H2122 cells by decreasing expression of both cPLA2 and COX-2. Finally, inhibitors of eicosanoid synthesis blocked anchorage-independent growth of NSCLC lines exhibiting Ki-Ras mutations. These results identify cPLA2 as a novel Ras-inducible regulator of eicosanoid synthesis that participates in cellular transformation.
Vaccination against Brucella. (1990)

Vaccination has played an enormous role in reducing brucellosis in many countries. It is certain to continue to be the preeminent factor in control of the disease in others. The search for an ideal vaccine continues. Live vaccines have proved to be superior to inactivated products. They are effective, inexpensive, and immunity is more persistent. The disadvantages of postvaccinal antibodies can be minimized by reduction of previously recommended doses and through use of supplemental diagnostic tests. These procedures now make entire population vaccination of great practical significance with many advantages over limited use of the strains 19 and Rev. 1. Adult animal vaccination should be much more extensive in many countries. A live B. suis strain 2 vaccine developed in China deserves much additional evaluation, including use in swine, for which no satisfactory vaccine exists. It is generally agreed that cell-mediated responses are the dominant aspect of immunogenesis. However, the correlates that have frequently been used--dermal hypersensitivity and lymphocyte stimulation in vitro--appear to be poor indices of cell-mediated immunity in brucellosis. Many studies have shown that postvaccinal antibodies do not predict subsequent immunity. There is a great need for simple in vivo or in vitro methods to measure CMI. While vaccination of humans may be useful in control of brucellosis in some high-risk occupations, the ultimate success is dependent upon reduction of this very important zoonosis in natural hosts. This is most effectively accomplished by widespread use of vaccination.
Effect of mutations K97A and E128A on RNA binding and self assembly of papaya mosaic potexvirus coat protein (2005)

Papaya mosaic potexvirus (PapMV) coat protein (CP) was expressed (CPdeltaN5) in Escherichia coli and showed to self assemble into nucleocapsid like particles (NLPs). Twenty per cent of the purified protein was found as NLPs of 50 nm in length and 80% was found as a multimer of 450 kDa (20 subunits) arranged in a disk. Two mutants in the RNA binding domain of the PapMV CP, K97A and E128A showed interesting properties. The proteins of both mutants could be easily purified and CD spectra of these proteins showed secondary and tertiary structures similar to the WT protein. The mutant K97A was unable to self assemble and bind RNA. On the contrary, the mutant E128A showed an improved affinity for RNA and self assembled more efficiently in NLPs. E128A NLPs were longer (150 nm) than the recombinant CPdeltaN5 and 100% percent of the protein was found as NLPs in bacteria. E128A NLPs were more resistant to digestion by trypsin than the CPdeltaN5 but were more sensitive to denaturation by heat. We discuss the possible role of K97 and E128 in the assembly of PapMV.