gebhart/patrepeval huggingface dataset:
Intrathecal CGRP8–37‐induced bilateral increase in hindpaw withdrawal latency in rats with unilateral inflammation (1996)

1. Recent work in our laboratory has demonstrated that intrathecal administration of a selective antagonist of calcitonin gene-related peptide (CGRP), CGRP8-37, increased the hindpaw withdrawal latency (HWL) to thermal stimulation and hindpaw withdrawal threshold (HWT) to pressure in normal rats, and that these effects were more pronounced than in rats with mononeuropathy. 2. The present study was performed to investigate the effects of intrathecal administration of CGRP8-37 on the HWL and HWT in rats with unilateral hindpaw inflammation induced by subcutaneous injection of carrageenin. The effect of naloxone was also studied. 3. Subcutaneous injection of 0.1 ml of carrageenin into the plantar region of the left hindpaw induced a significant increase in the volume of the ipsilateral hindpaw (P < 0.001), and significant bilateral decreases of the HWL to thermal stimulation (ipsilateral: P < 0.001; contralateral: P < 0.01) and HWT to pressure (ipsilateral: P < 0.001; contralateral: P < 0.01). 4. Intrathecal administration of 10 nmol of CGRP8-37, but not of 1 or 5 nmol, induced a significant bilateral increase in the HWL and HWT in rats with experimentally induced inflammation (thermal test: P < 0.001; mechanical test: P < 0.001). 5. The effect of intrathecal administration of 10 nmol CGRP8-37 on HWL and HWT was significantly more pronounced in intact rats than in rats with experimentally induced inflammation (ipsilateral: P < 0.001; contralateral: P < 0.001). 6. The effect of CGRP8-37 on withdrawal responses in the inflamed paw was partly reversed by intrathecal injection of naloxone at a dose of 88 nmol in the thermal (ipsilateral: P < 0.01; contralateral: P = 0.14) and mechanical tests (ipsilateral: P < 0.05; contralateral: P = 0.60). 7. A significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws was demonstrated 24 h after unilateral injection of carrageenin (ipsilateral: P < 0.001; contralateral: P < 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P < 0.001), but not in plasma (P = 0.75). 8. The present study demonstrates that acute experimentally-induced unilateral hindpaw inflammation, induces bilateral increases in the amount of CGRP-like immunoreactivity in hindpaw perfusates. Intrathecal administration of CGRP8-37 increased the HWL to thermal stimulation and HWT to pressure bilaterally. 9. The results indicate that CGRP plays a role in the transmission of presumed nociceptive information in the spinal cord of rats with experimentally induced inflammation. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.
Role of tumour necrosis factor stimulated gene 6 (TSG-6) in the coupling of inter-alpha-trypsin inhibitor to hyaluronan in human follicular fluid (2003)

Binding of the plasma proteinase inhibitor inter-alpha-trypsin inhibitor (ITI) to hyaluronan is necessary for normal expansion of the cumulus-oocyte complex. Lack of ITI causes severe infertility. Binding of ITI to hyaluronan depends on calcium ions and coupling activity present in follicular fluid (Odum et al., 2002). The complexes formed by this process contain ITI heavy chains bound to hyaluronan, and bikunin is detached from ITI during the coupling reaction. In the present study, an electrophoretic technique by which hyaluronan-bound ITI is immobilized was used to demonstrate that tumour necrosis factor stimulated gene 6 (TSG-6) is necessary for the coupling reaction. Thus, immunoprecipitation of TSG-6 in human follicular fluid eliminates the coupling reaction and re-addition restores the activity. However, it appears that components other than hyaluronan, ITI, calcium ions and TSG-6 are involved in the coupling reaction, as in vitro incubation of these components does not generate stable complexes between ITI heavy chains and hyaluronan unless some follicular fluid is added. In conclusion, TSG-6 is necessary for the coupling of ITI to hyaluronan, but at least one additional component in follicular fluid is essential.
The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry (2011)

Interest in developing diverse nanoparticle (NP)-biological composite materials continues to grow almost unabated. This is motivated primarily by the desire to simultaneously exploit the properties of both NP and biological components in new hybrid devices or materials that can be applied in areas ranging from energy harvesting and nanoscale electronics to biomedical diagnostics. The utility and effectiveness of these composites will be predicated on the ability to assemble these structures with control over NP/biomolecule ratio, biomolecular orientation, biomolecular activity, and the separation distance within the NP-bioconjugate architecture. This degree of control will be especially critical in creating theranostic NP-bioconjugates that, as a single vector, are capable of multiple functions in vivo, including targeting, image contrast, biosensing, and drug delivery. In this review, a perspective is given on current and developing chemistries that can provide improved control in the preparation of NP-bioconjugates. The nanoscale properties intrinsic to several prominent NP materials are briefly described to highlight the motivation behind their use. NP materials of interest include quantum dots, carbon nanotubes, viral capsids, liposomes, and NPs composed of gold, lanthanides, silica, polymers, or magnetic materials. This review includes a critical discussion on the design considerations for NP-bioconjugates and the unique challenges associated with chemistry at the biological–nanoscale interface—the liabilities of traditional bioconjugation chemistries being particularly prominent therein. Select bioorthogonal chemistries that can address these challenges are reviewed in detail, and include chemoselective ligations (e.g., hydrazone and Staudinger ligation), cycloaddition reactions in click chemistry (e.g., azide–alkyne cyclyoaddition, tetrazine ligation), metal-affinity coordination (e.g., polyhistidine), enzyme driven modifications (e.g., HaloTag, biotin ligase), and other site-specific chemistries. The benefits and liabilities of particular chemistries are discussed by highlighting relevant NP-bioconjugation examples from the literature. Potential chemistries that have not yet been applied to NPs are also discussed, and an outlook on future developments in this field is given.
Immunological response after therapeutic vaccination with WT1 mRNA-loaded dendritic cells in end-stage endometrial carcinoma. (2010)

This is the first patient with a WT1-positive endometrial carcinoma, to receive immunotherapy with WT1-RNA-loaded dendritic cells, resulting in a vaccine-specific T cell response.
[Effects of rosiglitazone on endothelium-dependent vasodilation in patients with Type 2 diabetes]. (2006)

Endothelium-dependent vasodilation function is impaired in patients with Type 2 diabetes. The therapy with rosiglitazone can increase the serum NO level, and improve endothelium-dependent vasodilation,but metformin has no influence on the above-mentioned indexes.
Time-based sampling of social network activity graphs (2010)

While most research in online social networks (OSNs) in the past has focused on static friendship networks, social network activity graphs are quite important as well. However, characterizing social network activity graphs is computationally intensive; reducing the size of these graphs using sampling algorithms is critical. There are two important requirements---the sampling algorithm must be able to preserve core graph characteristics and be amenable to a streaming implementation since activity graphs are naturally evolving in a streaming fashion. Existing approaches satisfy either one or the other requirement, but not both. In this paper, we propose a novel sampling algorithm called Streaming Time Node Sampling (STNS) that exploits temporal clustering often found in real social networks. Using real communication data collected from Facebook and Twitter, we show that STNS significantly out-performs state-of-the-art sampling mechanisms such as node sampling and Forest Fire sampling, across both averages and distributions of several graph properties.
Regulation of Progesterone Receptor Messenger Ribonucleic Acid in the Rat Medial Preoptic Nucleus by Estrogenic and Antiestrogenic Compounds: Anin SituHybridization Study (1997)

Progesterone receptor (PR) messenger RNA (mRNA) is concentrated in neurons of the preoptic area and other regions of the rat hypothalamus where it is colocalized with the estrogen receptor and regulated by changes in the steroid hormonal milieu. To date, little is known about the regulation of PR mRNA by estrogens and whether antiestrogenic compounds are capable of modulating its expression. The present studies used in situ hybridization to ascertain the time course of PR mRNA regulation in the medial preoptic nucleus by 17beta-estradiol, determine the effective dose required to elicit a response, and compare the efficacy of 17beta-estradiol with a variety of estrogenic or antiestrogenic compounds. The first series of studies revealed that the treatment of ovariectomized rats with 17beta-estradiol resulted in an increase in PR expression within 2 h, after which it remained elevated until 10 h postinjection and then returned to baseline levels. When ovariectomized rats were injected with 25-1000 ng/kg of 17beta-estradiol and euthanized 6 h later, a dose-dependent increase in the level of PR mRNA was observed, with a maximal response at 1000 ng/kg and an EC50 of 93.5 ng/kg. Subsequent studies evaluated the efficacy of a variety of estrogenic and antiestrogenic compounds in the rat preoptic nucleus. 17Beta-estradiol, diethylstilbestrol, and 17alpha-estradiol all significantly increased the level of PR mRNA, although the degree of induction varied with each compound. The injection of tamoxifen, raloxifene, toremifene, droloxifene, clomiphene, GW 5638, or ICI 182,780 had no significant estrogenic effect on PR gene expression at the dose evaluated. In contrast, when tamoxifen or raloxifene, but not ICI 182,780, was administered in the antagonist mode, a significant dose-related decrease in the estradiol-induced level of PR mRNA was seen in the preoptic area. The results of these studies clearly demonstrate that PR mRNA expression in the rat preoptic area is rapidly stimulated by a small dose of 17beta-estradiol. Moreover, the present report has also shown that the estrogenic nature of compounds such as tamoxifen, raloxifene, toremifene, droloxifene, clomiphene, and GW 5638 cannot be predicted by their activity in peripheral tissues. Together, the results of these studies provide important information about the central activity of estrogens and provide evidence for their tissue-specifc actions in the rat.
A tailed PCR procedure for cost‐effective, two‐order multiplex sequencing of candidate genes in polyploid plants (2012)

Complex polyploid crop genomes can be recalcitrant towards conventional DNA sequencing approaches for allele mining in candidate genes for valuable traits. In the past, this has greatly complicated the transfer of knowledge on promising candidate genes from model plants to even closely related polyploid crops. Next-generation sequencing offers diverse solutions to overcome such difficulties. Here, we present a method for multiplexed 454 sequencing in gene-specific PCR amplicons that can simultaneously address multiple homologues of given target genes. We devised a simple two-step PCR procedure employing a set of barcoded M13/T7 universal fusion primers that enable a cost-effective and efficient amplification of large numbers of target gene amplicons. Sequencing-ready amplicons are generated that can be simultaneously sequenced in pools comprising multiple amplicons from multiple genotypes. High-depth sequencing allows resolution of the resulting sequence reads into contigs representing multiple homologous loci, with only insignificant off-target capture of paralogues or PCR artefacts. In a case study, the procedure was tested in the complex polyploid genome of Brassica napus for a set of nine genes identified in Arabidopsis as candidates for regulation of seed development and oil content. Up to six copies of these genes were expected in B. napus. SNP discovery was performed by pooled multiplex sequencing of 30 amplicons in 20 diverse B. napus accessions with interesting trait variation for oil content, providing a basis for comparative mapping to relevant quantitative trait loci and for subsequent marker-assisted breeding.
Towards a Property-Based Testing Environment With Applications to Security-Critical Software (1994)

We consider an approach to testing that combines white-box and black-box techniques. Black-box testing is used for testing a program's effects against its specification. White-box testing is essential if subtle implementation errors are to be identified, e.g., errors due to race conditions. Full white-box testing is a large task. However, for many properties, only a small portion of the program is relevant hence property-based testing has the potential to substantially simplify much of the testing work. The portion of a program that relates to a given property can be identified through slicing. We describe the ongoing development of a Tester's Assistant, which in the long term, will include a specification-driven slicer for C programs, a test data generator, a coverage analyzer, an execution monitor. The slicer and execution monitor are described in this paper, and applications to Unix security are indicated. Security is an important application of property-based testing because of the subtle undetected security errors in delivered operating systems. It is also a promising application because of the (unexpectedly) concise specifications that capture most security requirements, and because of the operating system support for execution monitoring.
Elafibranor, an Agonist of the Peroxisome Proliferator−Activated Receptor−α and −δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening (2016)

A post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients' cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849.
Development of a bovine adenovirus type 3-based expression vector (1995)

We constructed a non-defective bovine adenovirus type 3 recombinant (BAd3-Luc) containing the firefly luciferase gene inserted in the early region 3 (E3) of the BAd3 genome. Deletion of a 696 bp XhoI-NcoI E3 segment and insertion of the luciferase gene in E3 was confirmed by Southern blot analyses. Luciferase was expressed in Madin-Darby bovine kidney cells infected with BAd3-Luc as measured by enzymic assays and Western blotting. Analyses of luciferase expression in the presence or absence of 1-beta-D-arabinofuranosylcytosine indicated that approximately 70-75% of luciferase expression was dependent on viral DNA replication, suggesting that transcription of the gene was at least partially under the control of a late promoter. Although yields of infectious virus for BAd3-Luc were approximately 10-fold lower than for wild-type virus, replication of the vector was still relatively efficient. In a Western blot experiment, anti-luciferase antibody reacted with a 62 kDa protein which is of the same molecular mass as the purified firefly luciferase polypeptide. Luciferase was also expressed in the 293 cell line infected with BAd3-Luc for at least 6 days post-infection as monitored by luciferase assays. Based on these observations we suggest that BAd-based expression vectors should have excellent potential for the development of recombinant vaccines for cattle and may also be suitable as vectors for gene transfer into human cells.
SIFT web server: predicting effects of amino acid substitutions on proteins (2012)

The Sorting Intolerant from Tolerant (SIFT) algorithm predicts the effect of coding variants on protein function. It was first introduced in 2001, with a corresponding website that provides users with predictions on their variants. Since its release, SIFT has become one of the standard tools for characterizing missense variation. We have updated SIFT's genome-wide prediction tool since our last publication in 2009, and added new features to the insertion/deletion (indel) tool. We also show accuracy metrics on independent data sets. The original developers have hosted the SIFT web server at FHCRC, JCVI and the web server is currently located at BII. The URL is http://sift-dna.org (24 May 2012, date last accessed).
A model of angiogenesis in the mouse cornea. (1996)

This noninflammatory model of corneal neovascularization is especially advantageous because it is reproducible, economical, and facilitates investigation of angiogenesis in various murine tumor models as well as in genetically defined murine strains.
Structured Design: Fundamentals of a Discipline of Computer Program and Systems Design (1979)

From the Publisher:
A valuable new approach to computer systems and program design, structured design is quickly becoming the standard industrial technique for significantly improving productivity, enhancing reliability, and lowering maintenance costs.
Convergence of the Iterative Hammerstein System Identification Algorithm (2004)

The convergence of the iterative identification algorithm for the Hammerstein system has been an open problem for a long time. In this paper, a detailed study is carried out and various convergence properties of the iterative algorithm are derived. It is shown that the iterative algorithm with normalization is convergent in general. Moreover, it is shown that convergence takes place in one step (two least squares iterations) for finite-impulse response Hammerstein models with i.i.d. inputs.
Reexamining the fault density component size connection (1997)

In software engineering, the lack of experimental evidence often means that anecdotal, intuitive, or sometimes just plain commercial arguments become surprisingly well-entrenched. Conventional wisdom, that smaller components contain relatively fewer faults may be wrong. The author found that medium-sized components were proportionately more reliable than small or large ones. Moreover, he says, there may be limits on the fault density we can achieve.
A third-order multistage sigma-delta modulator with reduced sensitivity to nonidealities (1991)

A multistage third-order sigma-delta modulator, which is unconditionally stable and has a low sensitivity to component mismatch and op-amp performance limitations, has been designed and fabricated in a 1.2- mu m CMOS double-poly technology. The modulator, consisting of cascaded second- and first-order stages, is scaled to prevent performance degradation from integrator overload. In addition, the first-stage integrator output is used directly, instead of its quantization error, to facilitate ratioless input circuitry in the second stage. Experimental results indicate a signal-to-noise ratio of 93 and 90 dB at a signal-to-distortion ratio of 93 dB for sample rates of 24 and 80 kHz, respectively.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins. (1991)

The antigen receptor expressed by mature T cells has been described as a disulfide-linked alpha/beta or gamma/delta heterodimer noncovalently associated with CD3, a complex of transmembrane proteins that communicates signals from the T cell receptor (TCR) to the cell interior. Studies suggest that all component chains must assemble intracellularly before surface expression can be achieved. We described, however, a CD4+/CD8+ transformed murine thymocyte, KKF, that expresses surface TCR-beta chains in the absence of gamma, delta, and alpha proteins; these beta chains are only weakly associated with CD3-epsilon and CD3-zeta. Furthermore, KKF responds differently to stimulation through TCR-beta and CD3-epsilon, a functional dissociation that has been ascribed to a CD4+/CD8+ subpopulation of normal thymocytes. KKF's unique TCR structure may offer an explanation for the functional anomalies observed.
Site‐specific incorporation of photofunctional nonnatural amino acids into a polypeptide through in vitro protein biosynthesis (1994)

Nonnatural amino acids with photofunctional groups were incorporated site-specifically into a polypeptide by using in vitro protein synthesizing system. The nonnatural amino acids were attached to tRNA(CCU) through chemical misacylation method, and added to the in vitro system with a mRNA containing a single AGG codon. L-p-Phenylazophenylalanine, L-2-anthrylalanine, L-1-naphthylalanine, L-2-naphthylalanine and L-p-biphenylalanine were successfully incorporated into a polypeptide, but l-1-pyrenylalanine was not. The polypeptides containing the nonnatural amino acids showed photofunctionalities.
Predictive Identification of Exonic Splicing Enhancers in Human Genes (2002)

Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed that predicts which sequences have ESE activity by statistical analysis of exon-intron and splice site composition. When large data sets of human gene sequences were used, this method identified 10 predicted ESE motifs. Representatives of all 10 motifs were found to display enhancer activity in vivo, whereas point mutants of these sequences exhibited sharply reduced activity. The motifs identified enable prediction of the splicing phenotypes of exonic mutations in human genes.
Androgen-induced remissions after antiestrogen and hypophysectomy in stage IV breast cancer (1981)

Fluoxymesterone (Halotestin), 10 mg p.o. BID, was given to 33 women with Stage IV breast cancer who had previously been treated wih the antiestrogen tamoxifen (Nolvadex) and of whom 17 had also undergone hypophysectomy. Objective remissions were obtained in 13 patients (39%) with an average duration of 11+ months. Response rate to fluoxymesterone was similar in patients who had previously responded to tamoxifen and in those who had failed. Duration of response was longer in the former group (12+ vs. 8 months), but this difference was not statistically significant. Of 17 patients who had been previously treated with tamoxifen and hypophysectomy, seven obtained further remission from fluoxymesterone for an average duration of ten months. Two patients with remissions from fluoxymesterone had previously failed to respond both to antiestrogen therapy and to the removal of the pituitary gland. Androgens appear to be an effective sequential endocrine treatment of Stage IV breast cancer after tamoxifen and hypophysectomy. The mechanism by which androgens induce tumor regression in some patients is probably not an antiestrogenic effect or an indirect effect mediated through the pituitary gland, but perhaps a direct action at the tumor level.
Smart channel assignment algorithm for SDMA systems (2002)

In order to exploit the potentialities of space division multiple access (SDMA) in mobile cellular systems the conventional radio resource management functions must be revised, especially the channel assignment algorithms. An algorithm designed to this purpose is presented and analysed in reference scenarios and under various traffic load conditions.