gebhart/patrepeval huggingface dataset:
Regulation of Bone Mass, Osteoclast Function, and Ovariectomy-Induced Bone Loss by the Type 2 Cannabinoid Receptor (2008)

The endocannabinoid system has recently been shown to play a role in the regulation of bone metabolism. The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass, but conflicting results have been reported with regard to its effects on bone resorption and osteoclast function. Here we investigated the role that CB2 plays in regulating bone mass and osteoclast function using a combination of pharmacological and genetic approaches. The CB2-selective antagonist/inverse agonist AM630 inhibited osteoclast formation and activity in vitro, whereas the CB2-selective agonists JWH133 and HU308 stimulated osteoclast formation. Osteoclasts generated from CB2 knockout mice (CB2-/-) were resistant to the inhibitory effects of AM630 in vitro, consistent with a CB2-mediated effect. There was no significant difference in peak bone mass between CB2-/- mice and wild-type littermates, but after ovariectomy, bone was lost to a greater extent in wild-type compared with CB2-/- mice. Furthermore, AM630 protected against bone loss in wild-type mice, but the effect was blunted in CB2-/- mice. We conclude that CB2 regulates osteoclast formation and bone resorption in vitro and that under conditions of increased bone turnover, such as after ovariectomy, CB2 regulates bone loss. These observations indicate that CB2 regulates osteoclast formation and contributes to ovariectomy-induced bone loss and demonstrate that cannabinoid receptor antagonists/inverse agonists may be of value in the treatment of bone diseases characterized by increased osteoclast activity.
Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel (2006)

The mitochondrial production of reactive oxygen species has been implicated in the anticancer activity of furanonaphthoquinone. However, the mechanism of the activation remains elusive. In the current study, we found that treatment of HeLa cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces mitochondrial swelling, followed by apoptosis. This toxic effect of FNQ13 was reduced by the radical scavengers alpha-tocopherol and trolox. Cytochemical experiments in isolated mitochondria showed that a combination of FNQ13 and NADH induces the production of H(2)O(2) at the exterior mitochondrial membrane surface. This production of H(2)O(2) was reduced by an antibody to the voltage-dependent anion channel (VDAC). Overexpression of the VDAC by transfection with vdac1 cDNA increased the production of H(2)O(2) by HeLa cells, whereas transfection with a small interfering RNA to VDAC reduced FNQ13-induced H(2)O(2) production and cell death due to an almost complete knockdown of VDAC expression. We also found significant correlations between the expression of VDAC and the induction of H(2)O(2) production and cell death by FNQ13 in 11 human cancer cell lines. These results indicate that the anticancer activity of furanonaphthoquinones depends on the production of reactive oxygen species by mitochondrial permeability transition pores including the VDAC.
Silencing of p16/CDKN2 expression in human gliomas by methylation and chromatin condensation. (1996)

The product of the p16/CDKN2 locus, p16ink4, negatively regulates the cell cycle through binding and inactivation of cyclin-dependent kinases (CDKs) 4 and 6. This locus is frequently targeted for deletion in cell lines and primary tumor tissues. In gliomas, although up to 50% do not have detectable expression of p16/CDKN2 protein or mRNA, often the gene is wild type in sequence. Here, we tested the hypothesis that transcriptional repression of p16/CDKN2 in gliomas may be mediated by aberrant methylation of the CpG island, which is in the 5' region of the locus. Partial rather than complete p16/CDKN2 methylation was detected in 24% (10 of 42) of the gliomas, regardless of tumor grade, but was not observed in normal brain (0 of 10). We tested whether this partial methylation could inhibit expression in a human tumor cell line in which suppressed p16/CDKN2 expression was associated with both methylation and tightly compacted chromatin around the p16/CDKN2 promoter. Exposure of these cells to 5-aza-2-deoxycytidine resulted in a dramatic increase in promoter accessibility and induction of p16/CDKN2 expression, indicating that chromatin structure, CpG island methylation, and p16/CDKN2 expression are intimately associated. Taken together, these data suggest that methylation occurs in only a subset of cells within gliomas and that the methylation-associated inactivation of p16/CDKN2 expression observed in many common human cancers may mechanistically result from structural changes in the chromatin containing the p16/CDKN2 locus.
Selection of a Plant-Bacterium Pair as a Novel Tool for Rhizostimulation of Polycyclic Aromatic Hydrocarbon-Degrading Bacteria (2001)

We developed a novel procedure for the selection of a microbe-plant pair for the stable and efficient degradation of naphthalene. Based on the rationale that root exudate is the best nutrient source available in soil, the grass (Lolium multiflorum) cultivar Barmultra was selected because of its abilities to produce a highly branched root system, root deeply, and carry a high population of Pseudomonas spp. bacteria on its roots. Starting with a mixture of total rhizobacteria from grass-like vegetation collected from a heavily polluted site and selecting for stable naphthalene degradation as well as for efficient root colonization, Pseudomonas putida strain PCL1444 was isolated. The strain's ability to degrade naphthalene was shown to be stable in the rhizosphere. Moreover, it had superior root-colonizing properties because, after the inoculation of grass seedlings, it appeared to colonize the root tip up to 100-fold better than the efficient root colonizer Pseudomonas fluorescens WCS365. Strain PCL1444 uses root exudate as the dominant nutrient source because the presence of grass seedlings in soil results in up to a 10-fold increase of PCL1444 cells. Moreover, the root colonized by strain PCL1444 was able to penetrate through an agar layer, resulting in the degradation of naphthalene underneath this layer. In addition, the inoculation of grass seeds or seedlings with PCL1444 protected them against naphthalene phytotoxicity. Finally, this plant-microbe combination appeared able to degrade naphthalene from soil that was heavily polluted with a complex mixture of polycyclic aromatic hydrocarbons. To our knowledge, this is the first time that a naturally occurring bacterium has been selected for the combination of the abilities to degrade a pollutant and colonize plant roots. We suggest that the principle described here, to select a bacterium which combines efficient root colonization with a beneficial activity, also can be used to improve the selection of other more efficient plant-bacterium pairs for beneficial purposes such as biocontrol, biofertilization, and phytostimulation.
An analysis of genetic variation inAstragalus cremnophylaxvar.cremnophylax, a critically endangered plant, using AFLP markers (1996)

A recently developed molecular technique (amplified fragment length polymorphisms, AFLP) was used for characterizing genetic heterogeneity within and among populations of a critically endangered species of plant, Astragalus cremnophylax var. cremnophylax. Using AFLP, up to 50 polymorphic genetic markers per AFLP-PCR amplification were generated, and a total of 220 variable markers overall. This information was used first to assess genetic diversity within each of the three known populations of Astragalus cremnophylax var. cremnophylax from Grand Canyon National Park in Arizona, USA: North Rim (NR; n = 970), South Rim Site 1 (SR1; n = 500), and South Rim Site 2 (SR2; n = 2). Diversity in the form of average heterozygosity [symbol: see text] H [symbol: see text] and the proportion of polymorphic genes [symbol: see text] P [symbol: see text] was greatest in the NR population ([symbol: see text] H [symbol: see text] = 0.13 and [symbol: see text] P [symbol: see text] = 0.38) and least in the SR2 population ([symbol: see text] H [symbol: see text] = 0.02 and [symbol: see text] P [symbol: see text] = 0.04). Diversity was also quite low for the SR1 population ([symbol: see text] H [symbol: see text] = 0.04 and [symbol: see text] P [symbol: see text] = 0.10). In addition, substantial genetic differentiation among populations was indicated by both phenetic (AMOVA) and genetic analyses (overall corrected FST = 0.41). This finding was corroborated by the results of several multivariate analyses which utilized the genetic data, including a UPGMA cluster analysis and a principal coordinate analysis which revealed the existence of discrete groups corresponding to the populations. Population structure was further revealed within the NR population which was known to consist of four spatially separated groups of plants. Several recommendations for the future management of the species are discussed.
Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers. (1998)

Defining the expression of tumor-associated antigens on primary and metastatic prostate cancer is the crucial first step in selecting appropriate targets for immune attack. In this study, the distribution of the tumor-associated antigens GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and metastatic prostate cancer and 16 types of normal tissues was compared by immunohistochemistry, using a panel of well-characterized monoclonal antibodies. Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9 metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were expressed on no more than three of nine metastatic specimens. Normal tissues were also tested with all antibodies. With regard to the eight antigens most widely expressed on prostate cancers, PSMA was not expressed significantly on any of the normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were more broadly distributed on normal epithelia, all primarily at the secretory borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was expressed on gray matter of brain. From the 30 antigens that we have screened, this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1, MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate cancer.
ZD1839 (Iressa™): For More Than Just Non-Small Cell Lung Cancer (2002)

ZD1839 (Iressa) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways involved in cell proliferation. Preclinical studies demonstrated that ZD1839 is a promising agent for the treatment of a wide range of tumors and has additive-to-synergistic effects when combined with radiation or chemotherapy in various cell lines and xenografts. Phase I clinical trials have reported that ZD1839 has acceptable tolerability and antitumor activity. In addition to non-small cell lung cancer, phase II/III studies are currently investigating ZD1839 as monotherapy or in combination therapy against prostate, breast, head and neck, gastric, and colorectal tumors.
MemC3: Compact and Concurrent MemCache with Dumber Caching and Smarter Hashing (2018)

This paper presents a set of architecturally and workload inspired algorithmic and engineering improvements to the popular Memcached system that substantially improve both its memory efficiency and throughput. These techniques—optimistic cuckoo hashing, a compact LRU-approximating eviction algorithm based uponCLOCK, and comprehensive implementation of optimistic locking—enable the resulting system to use 30% less memory for small key-value pairs, and serve up to 3x as many queries per second over the network. We have implemented these modiﬁcations in a system we call MemC3—Memcached with CLOCK and Concurrent Cuckoo hashing—but believe that they also apply more generally to many of today’s read-intensive, highly concurrent networked storage and caching systems.
Otolaryngology--head and neck surgery (1994)

p53 mutations are early events in the development of carcinoma of the head and neck. Cochlear implantation continues to influence rehabilitation of the profoundly deaf. Replacing cocaine with a combination of lidocaine and oxymetazoline for nasal procedures avoids potential abuse.
The Faces Pain Scale – Revised: toward a common metric in pediatric pain measurement (2001)

The Faces Pain Scale (FPS; Bieri et al., Pain 41 (1990) 139) is a self-report measure used to assess the intensity of children's pain. Three studies were carried out to revise the original scale and validate the adapted version. In the first phase, the FPS was revised from its original seven faces to six, while maintaining its desirable psychometric properties, in order to make it compatible in scoring with other self-rating and observational scales which use a common metric (0-5 or 0-10). Using a computer-animated version of the FPS developed by Champion and colleagues (Sydney Animated Facial Expressions Scale), psychophysical methods were applied to identify four faces representing equal intervals between the scale values representing least pain and most pain. In the second phase, children used the new six-face Faces Pain Scale-Revised (FPS-R) to rate the intensity of pain from ear piercing. Its validity is supported by a strong positive correlation (r=0.93, N=76) with a visual analogue scale (VAS) measure in children aged 5-12 years. In the third phase, a clinical sample of pediatric inpatients aged 4-12 years used the FPS-R and a VAS or the colored analogue scale (CAS) to rate pain during hospitalization for surgical and non-surgical painful conditions. The validity of the FPS-R was further supported by strong positive correlations with the VAS (r=0.92, N=45) and the CAS (r=0.84, N=45) in this clinical sample. Most children in all age groups including the youngest were able to use the FPS-R in a manner that was consistent with the other measures. There were no significant differences between the means on the FPS-R and either of the analogue scales. The FPS-R is shown to be appropriate for use in assessment of the intensity of children's acute pain from age 4 or 5 onward. It has the advantage of being suitable for use with the most widely used metric for scoring (0-10), and conforms closely to a linear interval scale.
Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase. (1981)

Oxidative degradation of biological substrates by hypochlorous acid has been examined under reaction conditions similar to those found in active phagosomes. Iron sulfur proteins are bleached extremely rapidly, followed in decreasing order by beta-carotene, nucleotides, porphyrins, and heme proteins. Enzymes containing essential cysteine molecules are inactivated with an effectiveness that roughly parallels the nucleophilic reactivities of their sulfhydryl groups. Other compounds, including glucosamines, quinones, riboflavin, and, except for N-chlorination, phospholipids, are unreactive. Rapid irreversible oxidation of cytochromes, adenine nucleotides, and carotene pigments occurs when bacterial cells are exposed to exogenous hypochlorous acid; with Escherichia coli, titrimetric oxidation of cytochrome was found to coincide with loss of aerobic respiration. The occurrence of these cellular reactions implicates hypochlorous acid as a primary microbicide in myeloperoxidase-containing leukocytes; the reactivity patterns observed are consistent with the view that bactericidal action results primarily from loss of energy-linked respiration due to destruction of cellular electron transport chains and the adenine nucleotide pool.
Chemoprevention of MNU-induced mammary tumorigenesis by hormone response modifiers: toremifene, RU 16117, tamoxifen, aminoglutethimide and progesterone. (1994)

The effects of structurally different antiestrogens, progesterone and the aromatase inhibitor aminoglutethimide, were evaluated for chemopreventive activity in the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model. Treatment with either RU 16117, progesterone or aminoglutethimide resulted in a significant decrease in cancer multiplicity [> or = 50%; P < .05] when administered individually at doses 80% of the maximally tolerated dose [MID]. Toremifene was also remarkably effective in inhibiting MNU-induced mammary tumorigenesis although this inhibition was achieved at a dose which caused a significant decrease in body weight gain. Aminoglutethimide, RU 16117 and toremifene citrate, in addition to their effects on tumor multiplicity, caused significant increases in the latency period for tumor development. Combinations of aminoglutethimide, progesterone and/or a suboptimal dose of tamoxifen citrate also proved to be effective in inhibiting the development of MNU-induced mammary cancers; however, the combination regimen was no more effective than either aminoglutethimide or progesterone administered alone. These results suggested that agents altering the hormonal environment, regardless of their mechanism of action, may provide protection against the development of hormone responsive mammary cancer.
Cre-mediated site-specific translocation between nonhomologous mouse chromosomes. (1995)

Chromosome rearrangements, such as large deletions, inversions, or translocations, mediate migration of large DNA segments within or between chromosomes, which can have major effects on cellular genetic control. A method for chromosome manipulation would be very useful for studying the consequences of large-scale DNA rearrangements in mammalian cells or animals. With the use of the Cre-loxP recombination system of bacteriophage P1, we induced a site-specific translocation between the Dek gene on chromosome 13 and the Can gene on chromosome 2 in mouse embryonic stem cells. The estimated frequency of Cre-mediated translocation between the nonhomologous mouse chromosomes is approximately 1 in 1200-2400 embryonic stem cells expressing Cre recombinase. These results demonstrate the feasibility of site-specific recombination systems for chromosome manipulation in mammalian cells in vivo, breaking ground for chromosome engineering.
Milatuzumab–SN-38 Conjugates for the Treatment of CD74+ Cancers (2013)

CD74 is an attractive target for antibody-drug conjugates (ADC), because it internalizes and recycles after antibody binding. CD74 mostly is associated with hematologic tumors but is expressed also in solid cancers. Therefore, ADCs of the humanized anti-CD74 antibody, milatuzumab, were examined for the therapy of CD74-expressing solid tumors. Milatuzumab-doxorubicin and two milatuzumab-SN-38 conjugates with cleavable linkers, differing in their stability in serum and how they release SN-38 in the lysosome, were prepared. CD74 expression was determined by flow cytometry and immunohistology. In vitro cytotoxicity and in vivo therapeutic studies were conducted in the human cancer cell lines A-375 (melanoma), HuH-7 and Hep-G2 (hepatoma), Capan-1 (pancreatic), NCI-N87 (gastric), and Raji Burkitt lymphoma. The milatuzumab-SN-38 ADC was compared with SN-38 ADCs prepared with anti-Trop-2 and anti-CEACAM6 antibodies in xenografts expressing their target antigens. Milatuzumab-doxorubicin was most effective in the lymphoma model, whereas in A-375 and Capan-1 solid tumors, only milatuzumab-SN-38 showed a therapeutic benefit. Despite much lower surface expression of CD74 than Trop-2 or CEACAM6, milatuzumab-SN-38 had similar efficacy in Capan-1 as anti-Trop-2-SN-38, but in NCI-N87, anti-CEACAM6 and anti-Trop-2 conjugates were superior. Studies in two hepatoma lines at a single dose level showed significant benefit over saline controls but not against an irrelevant immunoglobulin G conjugate. CD74 is a suitable target for ADCs in some solid tumor xenografts, with efficacy largely influenced by uniformity of CD74 expression and with SN-38 conjugates providing the best therapeutic responses; SN-38 conjugates were preferable in solid cancers, whereas doxorubicin ADC was better in lymphoma tested.
Revealing Gauguin (2009)

Designing technologies that support the explanation of museum exhibits is a challenging domain. In this paper we develop an innovative approach - providing a robot guide with resources to engage visitors in an interaction about an art exhibit. We draw upon ethnographical fieldwork in an art museum, focusing on how tour guides interrelate talk and visual conduct, specifically how they ask questions of different kinds to engage and involve visitors in lengthy explanations of an exhibit. From this analysis we have developed a robot guide that can coordinate its utterances and body movement to monitor the responses of visitors to these. Detailed analysis of the interaction between the robot and visitors in an art museum suggests that such simple devices derived from the study of human interaction might be useful in engaging visitors in explanations of complex artifacts.
Purification and Properties of Formaldehyde Dehydrogenase and Formate Dehydrogenase from Candida boidinii (1976)

Formaldehyde hydrogenase and formate dehydrogenase were purified 130-fold and 19-fold respectively from Candida boidinii grown on methanol. The final enzyme preparations were homogenous as judged by acrylamide gel electrophoresis and by sedimentation in an ultracentrifuge. The molecular weights of the enzymes were determined by sedimentation equilibrium studies and calculated as 80000 and 74000 respectively. Dissociation into subunits was observed by treatment with sodium dodecylsulfate. The molecular weights of the polypeptide chains were estimated to be 40000 and 36000 respectively. The NAD-linked formaldehyde dehydrogenase specifically requires reduced glutathione for activity. Besides formaldehyde only methylglyoxal served as a substrate but no other aldehyde tested. The Km values were found to be 0.25 mM for formaldehyde, 1.2 mM for methylglyoxal, 0.09 mM for NAD and 0.13 mM for glutathione. Evidence is presented which demonstrates that the reaction product of the formaldehyde-dehydrogenase-catalyzed oxidation of formaldehyde is S-formylglutathione rather than formate. The NAD-linked formate dehydrogenase catalyzes specifically the oxidation of formate to carbon dioxide. The Km values were found to be 13 mM for formate and 0.09 mM for NAD.
Single-pole-four-throw switch using high-aspect-ratio lateral switches (2004)

A single-pole-four-throw (SP4T) switch using a high-aspect ratio lateral metal-contact micromachined switch is reported. This simplified SP4T micromachined switch is developed using deep reactive ion etching fabrication technology based on silicon-on-insulator wafer. The measurement results of the SP4T switch show an insertion loss of less than 1 dB and isolation of 30 dB from DC to 6 GHz.
Mechanisms and Consequences of Lipid Peroxidation in Biological Systems (1985)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More