gebhart/patrepeval huggingface dataset:
Variations in cell form and cytoskeleton in human breast carcinoma cells in vitro. (1980)

Cell form and cytoskeletal organization were investigated in 13 human breast carcinoma cell lines in vitro. Using tubulin antibodies and indirect immunofluorescence to detect the arrangement of cytoplasmic microtubules, three distinct cell phenotypes were recognized: (a) cells with extensive arrays of microtubules (type 1); (b) cells which were diffusely stained with microtubules apparent only near the cell margins (type II intermediate); and (c) cells in which individual microtubules could not be detected and only diffuse fluorescence was apparent (type II diffuse). Type I cells were flattened epithelial-like cells, much like normal mammary epithelial cells, which when stained with actin antibody displayed many brightly fluorescent parallel cables or "stress fibers." Many microtubules and microfilament bundles were observed in type I cells when examined by transmission electron microscopy. Type II cells were more rounded, often grew in multilayered colonies, and displayed fewer microtubules and microfilament bundles when examined by either immunofluorescence or electron microscopy. Type II cells ranged from very small rounded cells with diffuse tubulin and actin immunofluorescence (type II diffuse) to more flattened cells in which microtubules and actin cables were observed near the flattened cell margins (type II intermediate). Since all of the cells were derived initially from malignant metastatic lesions and some were tumorigenic when injected into athymic nude mice, we assume that they remained malignant in vitro. Thus, in human breast carcinoma cells in vitro, it is not possible to associate any specific cell morphology or cytoskeletal phenotype with cancer or metastasis in vivo. Whether or not these same conclusions hold for breast tumor cells in situ remains to be determined.
Absorption and metabolism of oral progesterone. (1980)

The absorption, metabolism, and clearance of progesterone from the peripheral circulation were investigated in five postmenopausal women after oral administration of 100 mg daily for five consecutive days. Maximal plasma concentrations of progesterone were observed within four hours after ingestion of the last dose, when the range (22.11-34.18 nmol/l; 696-1077 ng/100 ml) was comparable with that observed during the mid-luteal phase of the ovarian cycle. The surge in values lasted six hours, and progesterone concentrations remained raised for at least 96 hours. Of the three metabolites studied, the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment, the peak values ranging from 1097 nmol/l (54.9 microgram/100 ml) to over 2000 nmol/l (100 microgram/100 ml), which was the upper limit of the assay used. Concentrations of 17-hydroxyprogesterone were least raised, and the peak values ranged from 4.32 to 9.68 nmol/l (143-319 ng/100 ml). The plasma profile of 20 alpha-dihydroprogesterone most closely approximated that of progesterone, although the range of maximal values was lower (7.11-16.06 nmol/l; 228-514 ng/100 ml). Plasma concentrations of oestradiol were unchanged by giving progesterone. It is concluded that the increases in circulating concentrations of progesterone and the biologically active metabolite 20 alpha-dihydroprogesterone, and the duration of these increases, were sufficient to modulate the biochemistry of responsive tissues. Oral progesterone may thus have a therapeutic role, and this route of administration merits further investigation.
Genomic interval engineering of mice identifies a novel modulator of triglyceride production (2000)

To accelerate the biological annotation of novel genes discovered in sequenced regions of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450-kb region on mouse chromosome 11, which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities, including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation, and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450-kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine, and hepatic triglyceride production is of particular importance because of the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.
Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations (2018)

The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.
New opportunities in drug design of metalloproteinase inhibitors: combination between structure–function experimental approaches and systems biology (2011)

We highlight the use of protein-based drug design strategies, for example, antibodies and protein scaffolds, targeting extracatalytic domains, which are central to proteolytic and non-proteolytic enzyme functions. Such rationally designed function-blocking inhibitors may create new opportunities in disease management and in emerging therapies that require control of dysregulated MMP activity without causing severe side effects. Importantly, the lessons learned from studying these protein-based inhibitors can be implemented to design new and effective small or medium sized synthetic antagonists.
Low-Cost FPGA Implementation of Volterra Series-Based Digital Predistorter for RF Power Amplifiers (2010)

This paper presents a low-complexity and low-cost hardware implementation of a Volterra series-based digital predistorter (DPD). This is achieved by introducing two novel model complexity reduction techniques into the system, namely, lookup table assisted gain indexing and time-division multiplexing for multiplier sharing. Experimental results show that this novel DPD implementation uses much less hardware resources, but still maintains excellent performance compared to conventional approaches.
The complete genome sequence ofMycobacterium aviumsubspeciesparatuberculosis (2005)

We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease.
Constituents of Cannabis Sativa (2014)

Abstract Cannabis (Cannabis sativa, or hemp) is an annual herbaceous plant belonging to the Cannabaceae family. This plant has been used for multiple purposes (medicinal, recreational, seed oil and industrial fiber, etc.) for thousands of years. Its psychoactive and physiologically active constituents, known as cannabinoids, are found in the flowers (and to a lesser extent the leaves, and minimally in the stems, and seeds). The cannabinoids, primarily Δ9-THC, are responsible for the plant's behavioral and psychotropic effects. There are also non-psychoactive cannabinoids such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG) which have several medicinal properties. The plant cannabis also contains other constituents which belong to diverse classes of natural products. To date there are 545 constituents reported in cannabis. Cannabis and the cannabinoids have potential medical applications in the treatment of a variety of serious illnesses. This chapter presents an overview of the phytochemistry of the cannabis plant and its chemical constituents with particular emphasis on the cannabinoids.
Methimazole Treatment of 262 Cats With Hyperthyroidism (1988)

The efficacy and safety of the antithyroid drug methimazole were evaluated over a 3-year period in 262 cats with hyperthyroidism. In 181 of the cats, methimazole was administered for 7 to 130 days (mean, 27.7 days) as a preoperative preparation for thyroidectomy. The remaining 81 cats were given methimazole for 30 to 1,000 days (mean, 228 days) as sole treatment for the hyperthyroid state. After 2 to 3 weeks of methimazole therapy (10 to 15 mg/d), the mean serum thyroxine (T4) concentration decreased significantly (P less than 0.001) from a pretreatment value of 12.1 micrograms/dl to 2.1 micrograms/dl. The final maintenance dose needed to maintain euthyroidism in the 81 cats that were given methimazole as sole treatment for hyperthyroidism ranged from 2.5 to 20 mg/d (mean, 11.9 mg/d). Clinical side effects developed in 48 (18.3%) cats (usually within the first month of therapy), which included anorexia, vomiting, lethargy, self-induced excoriation of the face and neck, bleeding diathesis, and icterus caused by hepatopathy. Mild hematologic abnormalities developed in 43 (16.4%) cats (usually within the first 2 months of treatment), which included eosinophilia, lymphocytosis, and slight leukopenia. In ten (3.8%) cats, more serious hematologic reactions developed including agranulocytosis and thrombocytopenia (associated with bleeding). These hematologic abnormalities resolved within 1 week after cessation of methimazole treatment. Immunologic abnormalities associated with methimazole treatment included the development of antinuclear antibodies in 52 of 238 (21.8%) cats tested and red cell autoantibodies (as evidenced by positive direct antiglobulin tests) in three of 160 (1.9%) cats tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Generation of deletion derivatives by targeted transformation of human-derived yeast artificial chromosomes. (1990)

Mammalian DNA segments cloned as yeast artificial chromosomes (YACs) can be manipulated by DNA-mediated transformation when placed in an appropriate yeast genetic background. A "fragmenting vector" has been developed that can introduce a yeast telomere and selectable marker into human-derived YACs at specific sites by means of homologous recombination, deleting all sequences distal to the recombination site. A powerful application of the method uses a human Alu family repeat sequence to target recombination to multiple independent sites on a human-derived YAC. Sets of deletion derivatives generated by this procedure greatly facilitate restriction mapping of large genomic segments. Targeting recombination with single copy sequences, such as cDNAs, will have many additional applications. This approach establishes a paradigm for manipulation and characterization of mammalian DNA segments cloned as YACs.
Composite structured light pattern for three-dimensional video (2003)

Based on recent discoveries, we introduce a method to project a single structured pattern onto an object and then reconstruct the three-dimensional range from the distortions in the reflected and captured image. Traditional structured light methods require several different patterns to recover the depth, without ambiguity or albedo sensitivity, and are corrupted by object movement during the projection/ capture process. Our method efficiently combines multiple patterns into a single composite pattern projection allowing for real-time implementations. Because structured light techniques require standard image capture and projection technology, unlike time of arrival techniques, they are relatively low cost.
Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome (2010)

In diploid mammalian genomes, parental alleles can exhibit different methylation patterns (allele-specific DNA methylation, ASM), which have been documented in a small number of cases except for the imprinted regions and X chromosomes in females. We carried out a chromosome-wide survey of ASM across 16 human pluripotent and adult cell lines using Illumina bisulfite sequencing. We applied the principle of linkage disequilibrium (LD) analysis to characterize the correlation of methylation between adjacent CpG sites on single DNA molecules, and also investigated the correlation between CpG methylation and single nucleotide polymorphisms (SNPs). We observed ASM on 23% approximately 37% heterozygous SNPs in any given cell line. ASM is often cell-type-specific. Furthermore, we found that a significant fraction (38%-88%) of ASM regions is dependent on the presence of heterozygous SNPs in CpG dinucleotides that disrupt their methylation potential. This study identified distinct types of ASM across many cell types and suggests a potential role for CpG-SNP in connecting genetic variation with the epigenome.
Ex vivo assay to determine the cyclooxygenase selectivity of non‐steroidal anti‐inflammatory drugs (1999)

1. In this study we describe experiments to establish ex vivo the selectivity of non-steroidal anti-inflammatory drugs (NSAIDs) given in vivo. 2. Anaesthetised (Inactin, 120 mg kg(-1)) male Wistar rats (220-250 g) received an i.v. dose of one of the following compounds (dose mg kg(-1)): aspirin (20), diclofenac (3), L-745,337 (30), nimesulide (15), salicylate (20), sulindac (10). Blood samples were taken before and up to 6 h after dosing and the plasma obtained from it was tested for its ability to inhibit prostanoid formation in IL-1beta-treated A549 cells (COX-2 system) and human washed platelets (COX-1 system). For control the same compounds were also added directly to the assay systems. 3. All drugs, except sodium salicylate, inhibited COX-1 and COX-2 when added directly to the test systems. Plasma from aspirin-treated rats was without effect on either COX-1 or COX-2, consistent with the rapid in vivo metabolism to salicylate. Conversely, plasma from sulindac-treated rats inhibited COX-1 and COX-2 with potencies according with in vivo metabolism to sulindac sulphide. Diclofenac was COX-1/2 non-selective when tested in vitro, but a slightly preferential inhibitor of COX-2 when tested ex vivo. Nimesulide was confirmed as preferential inhibitor of COX-2 both in vitro and ex vivo. L-745,337 was a selective COX-2 inhibitor when tested in vitro or ex vivo. 4. In conclusion, our experiments show clearly (a) NSAIDs inactivation, (b) activation of prodrugs, and (c) NSAIDs selectivity. Our assay provides useful information about the selectivity of NSAIDs that could be extended by the analysis of plasma samples taken from humans similarly treated with test drugs.
Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen (2004)

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env , gag , RT , rev , tat and nef , and MVA expressing HIV-1 IIIB nef , tat and rev and simian immunodeficiency virus (SIV) macJ5 gag / pol and vaccinia HIV-1 env , were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.
Circumventing dynamic modeling: evaluation of the error-state Kalman filter applied to mobile robot localization (2003)

The mobile robot localization problem is treated as a two-stage iterative estimation process. The attitude is estimated first and is then available for position estimation. The indirect (error state) form of the Kalman filter is developed for attitude estimation when applying gyro modeling. The main benefit of this choice is that combined dynamic modeling of the mobile robot and its interaction with the environment is avoided. The filter optimally combines the attitude rate information from the gyro and the absolute orientation measurements. The proposed implementation is independent of the structure of the vehicle or the morphology of the ground. The method can easily be transferred to another mobile platform provided it carries an equivalent set of sensors. The 2D case is studied in detail first. Results of extending the approach to the 3D case are presented. In both cases the results demonstrate the efficacy of the proposed method.
Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents (1965)

Several details of the assay of total phenolic substances have been investigated and an improved procedure developed. The improvements include the use of Folin-Ciocalteu reagent rather than the Folin-Denis reagent, gallic acid as a reference standard, and a more reproducible time-temperature color development period. The values obtained are less subject to variation and interference from several nonphenols, yet are directly comparable to the "tannin" values obtained by the previously standard method.
Can engineered bacteria help control cancer? (2001)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Five cardiac hormones decrease the number of human small‐cell lung cancer cells (2005)

Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.
Identification of anti‐CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization (2014)

A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody-derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98-expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope-immunized mouse spleen-derived antibody Fab library showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an undetectable minor population in mimotope-induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co-administration of adjuvant compounds such as T-cell epitope peptides and Toll-like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone.
Crystal Structure of the Mycobacterium tuberculosis P450 CYP121-Fluconazole Complex Reveals New Azole Drug-P450 Binding Mode (2006)

Azole and triazole drugs are cytochrome P450 inhibitors widely used as fungal antibiotics and possessing potent antimycobacterial activity. We present here the crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121 in complex with the triazole drug fluconazole, revealing a new azole heme ligation mode. In contrast to other structurally characterized cytochrome P450 azole complexes, where the azole nitrogen directly coordinates the heme iron, in CYP121 fluconazole does not displace the aqua sixth heme ligand but occupies a position that allows formation of a direct hydrogen bond to the aqua sixth heme ligand. Direct ligation of fluconazole to the heme iron is observed in a minority of CYP121 molecules, albeit with severe deviations from ideal geometry due to close contacts with active site residues. Analysis of both ligand-on and -off structures reveals the relative position of active site residues derived from the I-helix is a key determinant in the relative ratio of on and off states. Regardless, both ligand-bound states lead to P450 inactivation by active site occlusion. This previously unrecognized means of P450 inactivation is consistent with spectroscopic analyses in both solution and in the crystalline form and raises important questions relating to interaction of azoles with both pathogen and human P450s.