gebhart/patrepeval huggingface dataset:
Reactive oxygen species and antioxidants in inflammatory diseases (1997)

This paper aims to review the rôle of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases. There is a clearly defined and substantial role for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area. This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area. The recent discovery of the transcription factor nuclear factor kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-kappa B1 are discussed. Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon. The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits.
Ras farnesylation as a target for novel antitumor agents: Potent and selective farnesyl diphosphate analog inhibitors of farnesyltransferase (1995)

Abstract Protein prenylation is increasingly recognized as an important mechanism by which functional association of proteins to membranes is mediated. Ras proteins, regulators of cell proliferation and differentiation, are among the proteins that undergo farnesylation, one of the two prenylation modifications known. Since ras proteins are activated into hyperactive oncogenic versions in a wide variety of human cancers, agents that down modulate ras activity could be antineoplastic. Therefore, inhibitors of farnesyltransferase have the potential to be of therapeutic value as anticancer agents due to their ability to block ras processing and hence its function. We describe the identification of two farnesyl pyrophosphate (FPP) analogs that are potent and selective inhibitors of farnesyltransferase. While showing no toxicity to untransformed cells, a pivaloyloxymethyl ester of one of these inhibitors blocked ras mediated transformation of NIH 3T3 cells. In addition, both the ester and its parent acid inhibited ras farnesylation as measured by incorporation of labeled mevalonate into ras proteins in whole cells. Thus, this is the first report of an FPP analog to show biological activity by inhibiting ras processing in whole cells. © 1995 Wiley‐Liss, Inc.
Distinct Patterns of Dysregulated Expression of Enzymes Involved in Androgen Synthesis and Metabolism in Metastatic Prostate Cancer Tumors (2012)

Androgen receptor (AR) signaling persists in castration-resistant prostate carcinomas (CRPC), because of several mechanisms that include increased AR expression and intratumoral androgen metabolism. We investigated the mechanisms underlying aberrant expression of transcripts involved in androgen metabolism in CRPC. We compared gene expression profiles and DNA copy number alteration (CNA) data from 29 normal prostate tissue samples, 127 primary prostate carcinomas (PCa), and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by quantitative reverse transcriptase PCR in PCa cell lines and circulating tumor cells (CTC) from CRPC patients. Metastatic PCas expressed higher transcript levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased. This aberrant expression was rarely associated with CNAs. Instead, our data suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of the steroidogenic enzyme transcripts was detected in CTCs from CRPC patients. In conclusion, our findings identify substantial interpatient heterogeneity and distinct patterns of dysregulated expression of enzymes involved in intratumoral androgen metabolism in PCa. These steroidogenic enzymes represent targets for complete suppression of systemic and intratumoral androgen levels, an objective that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A comprehensive AR axis-targeting approach via simultaneous, frontline enzymatic blockade, and/or transcriptional repression of several steroidogenic enzymes, in combination with GnRH analogs and potent antiandrogens, would represent a powerful future strategy for PCa management.
Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. (1996)

Overexpression of the HER-2/neu proto-oncogene which encodes tyrosine kinase receptor p185neu, has been observed frequently in many human cancers, including non-small cell lung cancer (NSCLC), and is correlated with poor patient survival in these cancers. In addition, HER-2/neu overexpression in NSCLC is known to induce chemoresistance. Recently, we demonstrated that emodin, a tyrosine kinase inhibitor, suppresses HER-2/neu tyrosine kinase activity in HER-2/neu-overexpressing breast cancer cells and preferentially represses proliferation of these cells. The work described here was carried out to examine (1) whether the tyrosine kinase activity of p185neu is required for resistance to chemotherapeutic drugs of HER-2/neu-overexpressing NSCLC cells and (2) whether the tyrosine kinase inhibitor emodin can sensitize these cells to chemotherapeutic drugs. We found that emodin decreased tyrosine phosphorylation of HER-2/neu and preferentially suppressed proliferation of HER-2/neu-overexpressing NSCLC cells. Furthermore, the combination of emodin with cisplatin, doxorubicin or etoposide (VP16) synergistically inhibited the proliferation of HER-2/neu-overexpressing lung cancer cells, whereas low doses of emodin, cisplatin, doxorubicin, or VP16 alone had only minimal antiproliferative effects on these cells. These results indicate that tyrosine kinase activity is required for the chemoresistant phenotype of HER-2/neu-overexpressing NSCLC cells and that tyrosine kinase inhibitors such as emodin can sensitize these cells to chemotherapeutic drugs. The results may have important implications in chemotherapy for HER-2/neu-overexpressing cancers.
Hyperspeech: in Speech-Only Hypermedia (1991)

Most hypermedia systems emphasize the integration of graphics, images, video, and audio into a traditional hypertext framework. The hyperspeech system described in this paper, a speech-only hypermedia application, explores issues of navigation and system architecture in an audio environment without a visual display. The system under development uses speech recognition to maneuver in a database of digitally recorded speech segments; synthetic speech is used for control information and user feedback. In this research prototype, recorded audio interviews were segmented by topic, and hypertext-style links were added to connect logically related comments and ideas. The software architecture is data driven, with all knowledge embedded in the links and nodes, allowing the software that traverses through the network to be straightforward and concise. Several user interfaces were prototyped, emphasizing different styles of speech interaction and feedback between the user and machine. In addition to the issues of navigation in a speech-only database, areas of continuing research include: dynamically extending the database, use of audio and voice cues to indicate landmarks, and the simultaneous presentation of multiple channels of speech information.
The mechanism of action of amantadine in Parkinsonism: a review. (1975)

Studies of the mechanism of action of amantadine are reviewed. Data from pharmacological, behavioural and neurochemical experiments seem to indicate that the most likely effects of amantadine to be important in the alleviation of Parkinsonian symptoms are an indirect dopamine-releasing action and a direct stimulation of dopamine receptors. These effects may have a relative importance of approximately 4 : 1. Evidence favouring inhibition of dopamine uptake does exist, but the balance of opinion seems to be that this action is far too weak to contribute substantially to amantadine's action in vivo.
Validating speed of onset as a key component of good analgesic response in acute pain (2014)

In acute pain following third molar extraction, faster acting analgesic formulations provide earlier onset of pain relief, better overall pain relief and a less frequent need for additional analgesia, indicating longer lasting pain relief.
Glycoprotein H of Human Cytomegalovirus (HCMV) Forms a Stable Complex With The HCMV UL115 Gene Product (1992)

The human cytomegalovirus (HCMV) UL75 gene product is the homologue of herpes simplex virus type 1 (HSV-1) glycoprotein H (gH), a virion glycoprotein that is essential for infectivity and which is conserved among members of the alpha-, beta- and gamma-herpesviruses. It has previously been shown that HSV-1 gH forms a stable complex with HSV-1 gL, the product of the UL1 gene, and the formation of this complex facilitates the cell surface expression of gH. None of the open reading frames within the HCMV genome encode a product with discernible sequence homology with HSV-1 gL, but an examination of the arrangement of conserved genes in HCMV suggested that the UL115 gene is a 'positional homologue' of HSV-1 UL1 which, like UL1, encodes a small secreted glycoprotein. Co-expression of HCMV gH (the UL75 gene product) and the UL115 gene product revealed that these proteins form a disulphide-linked complex and that the formation of this complex results in cell surface expression of gH. This complex is analogous to the gH:gL complex of HSV-1 and the HCMV UL115 gene product is therefore the functional homologue of HSV-1 gL.
Juvenile rheumatoid arthritis (2007)

The diagnosis of juvenile rheumatoid arthritis (JRA) is based on patient's age at disease onset, symptom duration, gender, and clinical manifestations. JRA is of unknown origin, begins under the age of 16, and persists for a minimum of 6 weeks. JRA is categorized into three principal types, systemic, oligoarticular and polyarticular. Infection, other connective tissue diseases, malignancy, trauma, and immunodeficiency are discussed as differential diagnoses for JRA. Because of joint damage, focusing on early diagnosis and intervention, a vigorous initial therapeutic approach must be taken in patients who have poor prognostic factors. A multidisciplinary team approach is also important for the care of patients with JRA.
Neoteric pharmacotherapeutic targets in fibromyalgia (2011)

Current research on novel sedative-hypnotics, anti-epileptic medications, various reuptake inhibitors, growth hormone agonists, canabinoid agonists, non-opiate analgesics and 5-HT3 antagonists offers hope for the the next generation of therapeutic options for fibromyalgia. With regards to the development of novel pharmacotherapies, there seem to be grounds for increased optimism regarding prospective treatments of the disorder.
Direction finding on spread-spectrumsignals using the time-domain filtered cross spectral density (1997)

In an earlier paper, it was shown that spread-spectrum signals of arbitrary unknown waveform could be detected at received powers well below the receiver noise level, by crosscorrelating the signals from two spatially separated antennas, windowing the crosscorrelation function (CCF) over a narrow range about zero time shift and taking its Fourier transform, thus forming the time-domain-filtered cross spectral density (TDFCSD). The authors show that, having detected the signal and established its bandwidth, it is possible to estimate its angle of arrival (AOA) by measuring the phase slope in the TDFCSD across the signal bandwidth. An analysis of the technique is presented showing how the direction finding (DF) accuracy varies with signal and receiver parameters. Computer simulation results show that, with an antenna spacing as low as 1 m, a DF error of less than 1° can be obtained on a signal with a bandwidth of 100 MHz at a received power level lower than –100 dBm, using an integration time of a few milliseconds. A practical system based upon an acousto-optic correlator capable of computing the CCF in real time is described. Preliminary results from the system show DF errors that are in good agreement with theory.
Differential hygienic behaviour towardsVarroa jacobsoniin capped worker brood ofApis ceranadepends on alien scent adhering to the mites (1993)

SUMMARYFive Apis cerana colonies in Newton hives in Allahabad, northern India, were used in the experiments. Female Varroa jacobsoni, in the reproductive phase, were transferred from drone brood into worker brood in the same colony (1), or into worker brood in another colony (2). Some introductions (3) involving dead mites washed with ethanol and pentane (and therefore odour-free) were also carried out. Mites collected from a single Apis mellifera colony were introduced into some A. cerana brood (4), and some ‘sham inoculations’, involving the opening and closing of brood cells without the introduction of a mite, were made (5). After 5 days, in (1) and (5) only about 10% of manipulated cells were found empty. In (1) and (3), in addition, about 40% of cells had been opened, the mites removed, and the cells, still containing pupae, resealed. About 50% of manipulated cells were untouched. The percentage of empty cells was much higher in (2), and even higher in (4). The results indicate that differences in hygienic behaviour are due to scent cues adhering to the mites. The incidence of this type of behaviour in the Apis mellifera colony was extremely low. The significance of the differential hygienic behaviour observed in the tolerance of V. jacobsoni infestations is discussed.
Characterizing heterogeneity in children with and without ADHD based on reward system connectivity (2015)

One potential obstacle limiting our ability to clarify ADHD etiology is the heterogeneity within the disorder, as well as in typical samples. In this study, we utilized a community detection approach on 106 children with and without ADHD (aged 7-12 years), in order to identify potential subgroups of participants based on the connectivity of the reward system. Children with ADHD were compared to typically developing children within each identified community, aiming to find the community-specific ADHD characteristics. Furthermore, to assess how the organization in subgroups relates to behavior, we evaluated delay-discounting gradient and impulsivity-related temperament traits within each community. We found that discrete subgroups were identified that characterized distinct connectivity profiles in the reward system. Importantly, which connections were atypical in ADHD relative to the control children were specific to the community membership. Our findings showed that children with ADHD and typically developing children could be classified into distinct subgroups according to brain functional connectivity. Results also suggested that the differentiation in "functional" subgroups is related to specific behavioral characteristics, in this case impulsivity. Thus, combining neuroimaging data and community detection might be a valuable approach to elucidate heterogeneity in ADHD etiology and examine ADHD neurobiology.
Screening for thermostable mutant of kanamycin nucleotidyltransferase by the use of a transformation system for a thermophile, Bacillus stearothermophilus. (1985)

A structural gene of kanamycin nucleotidyltransferase cloned into a single-stranded bacteriophage M13 was subjected to mutagenesis with hydroxylamine. Having recloned the mutagenized gene of the enzyme in a vector plasmid pTB922, the recombinant plasmid was used to transform Bacillus stearothermophilus with a purpose of screening for the more thermostable enzyme than the wild type. Out of greater than 8 X 10(3) transformants, 12 clones that were suspected to harbor the mutant gene encoding the more thermostable enzyme were isolated by shifting from a permissive (55 degrees C) to a nonpermissive (61 degrees C) temperature that inactivates the wild-type enzyme. DNA sequence analysis of the mutant genes revealed two types of mutation of single base substitution and hence a single amino acid replacement. The first type was the replacement of an aspartate by a tyrosine at position 80 of the wild-type enzyme, while the second was that of a threonine by a lysine at position 130. Purified enzymes from the two mutant genes were confirmed to be substantially more thermostable than the wild type in vitro. The method of screening for a thermostable kanamycin nucleotidyltransferase presented here could be applied to any other enzyme, if a transformation system of a thermophile were available. Indeed, thermostable mutants with a subtle amino acid change would be of value for better understanding of forces and interactions that contribute to the stability of a protein.
The CEPH YAC library. (1992)

Because of their large size, YACs provide is a powerful tool for physical mapping studies of complex genomes. As it will be advantageous to have genomic libraries of clones with large inserts for analyzing megabase sized regions of the human genome, we have investigated a number of parameters in order to increase the insert size of the YACs. We constructed a genomic library currently containing more than 85,000 YAC clones. Mean sizes of YACs produced at several stages of construction of the library range from 430 kb to 1,200 kb, representing 13 haploid equivalents of the human genome. This library was organized in order to allow rapid screen of YACs for large scale physical mapping of the human genome.
Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors (2002)

The use of cervical spine interbody fusion cages coated with PDLLA as a delivery system for growth factors was effective. In this 12-week follow-up study, the PDLLA coating showed no adverse effects. The slight but not significant positive effect of the PDLLA carrier on interbody fusion might be a result of the degradation process of the biodegradable carrier. Compared with collagen sponge delivery of BMP-2, the PDLLA-coated interbody cages significantly increased the results of interbody bone matrix formation. In this new combination (implant + PDLLA + growth factor) the cage represents a "real fusion" cage, because it not only serves as a mechanical device for spinal fixation but also as a local drug delivery system.
Managing wound pain in patients with vacuum-assisted closure devices. (2002)

The etiology and management of wound pain for patients with vacuum-assisted closure devices can be complex. Patients, such as the patient with necrotizing fasciitis described in this case study, may experience all three types of pain described in the Chronic Wound Pain Experience Model--acute noncyclic, acute cyclic, and chronic. Strategies that include local wound management to reduce all three types of pain and holistic psychological care to reduce the ache and anguish that may accompany dressing change procedures may help provide comfort and reduce pain and suffering.
Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI (2008)

Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.
The placenta: transcriptional, epigenetic, and physiological integration during development (2010)

The placenta provides critical transport functions between the maternal and fetal circulations during intrauterine development. Formation of this interface relies on coordinated interactions among transcriptional, epigenetic, and environmental factors. Here we describe these mechanisms in the context of the differentiation of placental cells (trophoblasts) and synthesize current knowledge about how they interact to generate a functional placenta. Developing an understanding of these pathways contributes to an improvement of our models for studying trophoblast biology and sheds light on the etiology of pregnancy complications and the in utero programming of adult diseases.
Realization of a near-perfect antireflection coating for silicon solar energy utilization (2008)

To harness the full spectrum of solar energy, Fresnel reflection at the surface of a solar cell must be eliminated over the entire solar spectrum and at all angles. Here, we show that a multilayer nanostructure having a graded-index profile, as predicted by theory [J. Opt. Soc. Am. 66, 515 (1976); Appl. Opt. 46, 6533 (2007)], can accomplish a near-perfect transmission of all-color of sunlight. An ultralow total reflectance of 1%-6% has been achieved over a broad spectrum, lambda = 400 to 1600 nm, and a wide range of angles of incidence, theta = 0 degrees-60 degrees . The measured angle- and wavelength-averaged total reflectance of 3.79% is the smallest ever reported in the literature, to our knowledge.
MicroRNA-451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor (2016)

Neuroblastoma (NB) is the most prevalent type of extracranial solid tumour in young children. To improve current understanding of the mechanisms, which modulate cancer cell proliferation, invasion and migration, investigations have focused on microRNAs (miRs), a class of small non‑coding RNAs, which post‑transcriptionally regulate gene expression during various crucial cell processes. The present study aimed to investigate the role of miR‑451 in NB. Human NB tissue and adjacent normal tissue were surgically removed, and the expression of miR‑451, and development and pathological characteristics of NB were investigated. The expression of miR‑451 was reduced in the NB tissue, compared with that in the adjacent tissue, and correlations between the reduction in miR‑451 and unfavourable variables included tumour size (P=0.0081), differentiation (P=0.0217), lymph node metastasis (P=0.0489), tumour‑node‑metastasis stage (0.0220) and distant metastases (P=0.0201). Transfection of the SK‑N‑SH and GI‑LA‑N NB cell lines with miR‑451 inhibited cell growth, invasion and migration. Furthermore, the present study demonstrated that macrophage migration inhibitory factor (MIF) was regulated directly by miR‑451 and was a critical mediator of the biological effects of miR‑451 in NB. The re‑expression of MIF markedly reversed the carcinogenic inhibitory property of miR‑451. These data provide a more detailed understanding of the essential role of miR‑451 in NB, which relies on regulation of the expression of MIF.