gebhart/patrepeval huggingface dataset:
Abstract C208: CCT129254 (AT11854) is a well tolerated, orally bioavailable inhibitor of AKT/PKB with pharmacodynamic and antitumor activity in a range of xenograft models (2009)

Abstract The PI3K/AKT/mTOR pathway is the most frequently deregulated pathway in human cancer. The serine/threonine kinase AKT (PKB), a member of the AGC family of protein kinases, is central to this pathway and is considered an important target for cancer therapy. However, the development of well tolerated, orally bioavailable inhibitors of catalysis targeting this enzyme has proved challenging and there are currently no such agents that have progressed to phase II clinical studies. We have characterised the pharmacodynamic and anti-tumor activity of CCT129254, a small molecule inhibitor of AKT. CCT129254 was well tolerated when dosed chronically at up to 200 mg/kg qd in nude mice. Acute doses of 100–200 mg/kg CCT129254 caused dose-dependent transient elevations of blood glucose concentration and inhibition of AKT substrate phosphorylation in xenografts. An acute dose of 200 mg/kg qd CCT129254 significantly reduced pGSK3 for &amp;gt;6h in U87-MG xenografts, and this pharmacodynamic activity correlated with plasma drug concentration. Moreover, chronic dosing of CCT129254 caused a dose-dependent inhibition of tumor growth in this model. Chronic once daily dosing of CCT129254 significantly inhibited tumor growth in 14 of 16 other xenograft models, including breast, prostate, lung, ovarian, kidney and colon. The highest single agent activity was seen in two breast cancer xenografts (BT474c and HCC-1954). Significant activity was also seen in the gefitinib-resistant NCI-H1975 NSCLC model with respectively activating and resistance L858R and T790M mutations in EGFR. Increased efficacy is also seen when CCT129254 is combined with the cytotoxic agents cisplatin, doxorubicin and taxotere in xenograft models. CCT129254 exemplifies an oral, well tolerated inhibitor of AKT catalysis with the potential to inhibit the growth of a wide range of solid tumors both as monotherapy and in combination with cytotoxic agents. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C208.
Pilot study of dermal and subcutaneous fat structures by MRI in individuals who differ in gender, BMI, and cellulite grading (2004)

MR images can be interpreted to measure tissue parameters correlated with cellulite. Considering that we had only three subjects in each group, the achievements of this pilot study were highly satisfactory. We have shown that the in vivo micro-MR is a technique able to detect the effects of cellulite and gender. This study can be extended for further investigations of drugs and/or medical devices for cellulite treatment.
Prolonged Survival and Remyelination After Hematopoietic Cell Transplantation in the Twitcher Mouse (1984)

The twitcher mouse is an animal model of galactosylceramidase deficiency (Krabbe's disease), a human sphingolipidosis. The effects of hematopoietic cell transplantation as potential enzyme replacement therapy were examined in the twitcher mouse. Survival in twitcher mice with transplants was significantly prolonged and was associated with gradual repair of demyelination in peripheral nerves. In contrast, there was no improvement in the neurodegenerative process in the central nervous system after transplantation. These observations indicate that cellular transplantation may effectively provide in vivo enzyme replacement for the peripheral manifestations of genetic storage diseases. Strategies to perturb the blood-brain barrier may be necessary for enzyme replacement to be therapeutic in diseases with central nervous system manifestations.
Effect of p40 tax trans -Activator of Human T Cell Lymphotropic Virus Type I on Expression of Autoantigens (1994)

The possibility of a retroviral etiology has long been raised in a number of autoimmune disorders. More recently, Sjögren's syndrome and rheumatoid arthritis were noted in transgenic mice carrying the tax gene of human T cell leukemia virus type I (HTLV-I). To evaluate the involvement of HTLV-I Tax in autoimmunity, its effect on expression of autoantigens was investigated. A metallothionein promoter-driven p40tax expression plasmid, pMAXRHneo-1, was stably transfected into Molt4 and Jurkat cells and the p40tax protein was induced with CdCl2. trans-Activation or trans-repression of autoantigens by HTLV-I Tax was studied by Western blot analysis utilizing autoantigen-specific murine monoclonal and rabbit polyvalent antibodies as well as sera from 161 autoimmune patients. Induction of p40tax of HTLV-I had no significant effect on levels of expression of common autoantigens U1 snRNP, Sm, Ro, La, HSP-70, topoisomerase I/Scl70, PCNA, and HRES-1. Expression of two potentially novel autoantigens, 44 and 46 kDa, was induced by p40tax as detected by sera of progressive systemic sclerosis patients, BAK and VAR. By contrast, expression of 24- and 34-kDa proteins was suppressed in response to induction of p40tax as detected by sera of systemic lupus erythematosus patients PUS and HOR. Because none of these patients were infected by HTLV-I, a protein functionally similar to p40tax may be involved in eliciting autoantigen expression and a subsequent autoantibody response in a minority of patients with PSS and SLE. Sera of autoimmune patients may also be utilized to detect novel proteins trans-activated or trans-repressed by p40tax of HTLV-I.
Breaking the 10-7 Barrier for RI Measurements in Nanoliter Volumes (2002)

Refractive index (RI) detection is a common technique used in chemical and biochemical analysis. It can be employed to perform universal solute detection in microHPLC and CE, as well as temperature measurements. However, accurate RI measurements in nanoliter volumes still present a significant challenge. Here we present an alternative method to extract RI information encoded in spatial distribution of the backscattered fringes produced by a microinterferometric backscatter detector (MIBD) based on spatial Fourier analysis. By monitoring the phase in the Fourier domain, we were able to obtain detection limits of 7 x 10(-8) RIU. It was also shown that such calculations could be performed in real time, thus making MIBD with Fourier analysis compatible with microHPLC, CE, and FIA.
A Theory of Auctions and Competitive Bidding (1982)

Abstract : In Section 2, we review some important results of the received auction theory, introduce a new general auction model, and summarize the results of our analysis. Section 3 contains a formal statement of our model, and develops the properties of affiliated random variables. The various theorems are presented in Sections 4-8. In Section 9, we offer our views on the current state of auction theory. Following Section 9 is a technical appendix dealing with affiliated random variables.
Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY (2014)

Mutation-induced activation of splice sites in intronic repetitive sequences has contributed significantly to the evolution of exon-intron structure and genetic disease. Such events have been associated with mutations within transposable elements, most frequently in mutation hot-spots of Alus. Here, we report a case of Alu exonization resulting from a 367-nt genomic COL4A5 deletion that did not encompass any recognizable transposed element, leading to the Alport syndrome. The deletion brought to proximity the 5' splice site of COL4A5 exon 33 and a cryptic 3' splice site in an antisense AluY copy in intron 32. The fusion exon was depleted of purines and purine-rich splicing enhancers, but had low levels of intramolecular secondary structure, was flanked by short introns and had strong 5' and Alu-derived 3' splice sites, apparently compensating poor composition and context of the new exon. This case demonstrates that Alu splice sites can be activated by outlying deletions, highlighting Alu versatility in shaping the exon-intron organization and expanding the spectrum of mutational mechanisms that introduce repetitive sequences in mRNAs.
Chemistry of Amino Acids and Peptides (1959)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Biosynthesis of the Macrolide Oleandomycin by Streptomyces antibioticus (1995)

The oleandomycin (OM) producer, Streptomyces antibioticus, possesses a mechanism involving two enzymes for the intracellular inactivation and extracellular reactivation of the antibiotic. Inactivation takes place by transfer of a glucose molecule from a donor (UDP-glucose) to OM, a process catalyzed by an intracellular glucosyltransferase. Glucosyltransferase activity is detectable in cell-free extracts concurrent with biosynthesis of OM. The enzyme has been purified 1,097-fold as a monomer, with a molecular mass of 57.1 kDa by a four-step procedure using three chromatographic columns. The reaction operates via a compulsory-order mechanism. This has been shown by steady-state kinetic studies using either OM or an alternative substrate (rosaramycin) and dead-end inhibitors, and isotopic exchange reactions at equilibrium. OM binds first to the enzyme, followed by UDP-glucose. A ternary complex is thus formed prior to transfer of glucose. UDP is then released, followed by the glycosylated oleandomycin (GS-OM). The oleandomycin (OM) producer, Streptomyces antibioticus, possesses a mechanism involving two enzymes for the intracellular inactivation and extracellular reactivation of the antibiotic. Inactivation takes place by transfer of a glucose molecule from a donor (UDP-glucose) to OM, a process catalyzed by an intracellular glucosyltransferase. Glucosyltransferase activity is detectable in cell-free extracts concurrent with biosynthesis of OM. The enzyme has been purified 1,097-fold as a monomer, with a molecular mass of 57.1 kDa by a four-step procedure using three chromatographic columns. The reaction operates via a compulsory-order mechanism. This has been shown by steady-state kinetic studies using either OM or an alternative substrate (rosaramycin) and dead-end inhibitors, and isotopic exchange reactions at equilibrium. OM binds first to the enzyme, followed by UDP-glucose. A ternary complex is thus formed prior to transfer of glucose. UDP is then released, followed by the glycosylated oleandomycin (GS-OM).
CIB1, a Ubiquitously Expressed Ca2+-binding Protein Ligand of the InsP3 Receptor Ca2+ Release Channel (2006)

A family of Ca(2+)-binding proteins (CaBPs) was shown to bind to the inositol 1,4,5-trisphosphate receptor (InsP(3)R) Ca(2+) release channel and gate it in the absence of InsP(3), establishing them as protein ligands (Yang, J., McBride, S., Mak, D.-O. D., Vardi, N., Palczewski, K., Haeseleer, F., and Foskett, J. K. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7711-7716). However, the neuronally restricted expression of CaBP and its inhibition of InsP(3)R-mediated Ca(2+) signaling when overexpressed (Kasri, N. N., Holmes, A. M., Bultynck, G., Parys, J. B., Bootman, M. D., Rietdorf, K., Missiaen, L., McDonald, F., De Smedt, H., Conway, S. J., Holmes, A. B., Berridge, M. J., and Roderick, H. L. (2004) EMBO J. 23, 312-321; Haynes, L. P., Tepikin, A. V., and Burgoyne, R. D. (2004) J. Biol. Chem. 279, 547-555) have raised questions regarding the functional implications of this regulation. We have discovered the Ca(2+)-binding protein CIB1 (calmyrin) as a ubiquitously expressed ligand of the InsP(3)R. CIB1 binds to all mammalian InsP(3)R isoforms in a Ca(2+)-sensitive manner dependent on its two functional EF-hands and activates InsP(3)R channel gating in the absence of InsP(3). In contrast, overexpression of CIB1 or CaBP1 attenuated InsP(3)R-dependent Ca(2+) signaling, and in vitro pre-exposure to CIB1 reduced the number of channels available for subsequent stimulation by InsP(3). These results establish CIB1 as a ubiquitously expressed activating and inhibiting protein ligand of the InsP(3)R.
High throughput slotted ALOHA packet radio networks with adaptive arrays (1993)

The authors consider the use of a multiple-beam adaptive array (MBAA) in a packet radio system. In an MBAA, a given set of antenna elements is used to form several antenna patterns simultaneously. When it is used in a packet radio system, an MBAA can successfully receive two or more overlapping packets at the same time. Each beam captures a different packet by automatically pointing its pattern toward one packet while nulling other, contending packets. It is shown how an MBAA can be integrated into a single-hop slotted ALOHA packet radio system, and the resulting throughput is analyzed for both finite- and infinite-user populations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
BER performance improvement by forward error correctingcodein 5 Gbit/s 9000 km EDFA transmission system (1994)

Forward error correction (FEC) has been used to improve the bit error rate pertormance of a 5 Gbit/s 9000 km erbium-doped fibre amplifier (EDFA) transmission line. The results using a 5 Gbit/s prototype optical transmission terminal showed extremely small penalty in BER performance after 9000 km transmission.
Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small-cell lung cancer. (2000)

Patients with unresectable non-small-cell lung cancer (NSCLC) usually have undergone chemotherapy; however, such problems as resistance to chemotherapeutic agents occur during the treatments. Recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. We examined a possible relationship between immunohistochemical expression of GST-pi and the response to cisplatin plus etoposide chemotherapy in patients with untreated and unresectable primary NSCLC. Of the 89 patients, 50 (56.2%) were GST-pi-positive and 39 (43.8%) were GST-pi-negative. For the patients with negative GST-pi expression, the response rate was 66.7% (26 of 39 patients). In the patients with positive GST-pi expression, the response rate was 26% (13 of 50 patients). This difference was statistically significant (P = .0019). The results suggest that GST-pi expression in NSCLC tissues is related to response to cisplatin plus etoposide chemotherapy and may be useful as a predictor of chemotherapy response.
Use of a peripheral perfusion index derived from the pulse oximetry signal as a noninvasive indicator of perfusion (2002)

The peripheral perfusion index distribution in the normal population is highly skewed. Changes in the peripheral perfusion index reflect changes in the core-to-toe temperature difference. Therefore, peripheral perfusion index measurements can be used to monitor peripheral perfusion in critically ill patients.
Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis (2019)

The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation of NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) in Kras<sup>G12D</sup>-driven serrated cancer. Transcriptional profiling reveals that epithelial NOTCH1 signaling creates a tumor microenvironment (TME) reminiscent of poorly prognostic human CRC subtypes (CMS4 and CRIS-B), and drives metastasis through transforming growth factor (TGF) β-dependent neutrophil recruitment. Importantly, inhibition of this recruitment with clinically relevant therapeutic agents blocks metastasis. We propose that NOTCH1 signaling is key to CRC progression and should be exploited clinically.
Measurement of mechanical properties of ligament substance from a bone‐ligament‐bone preparation (1983)

This investigation presents a new approach in the measurement of the mechanical properties of the ligament substance from tensile testing of a bone-ligament-bone complex. Such basic information should be one of the necessary prerequisites in the evaluation of ligament repair as well as reconstruction by autogenous tissue grafts or artificial ligament implants. The use of a video system permits the determination of tensile strains of the mid-medial collateral ligaments from the canine, swine, and rabbit without mechanically interfering with the ligament deformation during testing. This methodology further eliminates the difficulties of measuring the initial length of the entire medial collateral ligament, as its insertions to bones are ambiguous and cover a large area. It was found that the strain of the ligament substance is consistently and considerably less than specific deformation of the bone-ligament-bone complex. These data suggest that the ligament-bone structure stretches nonuniformly with the highest deformation occurring near or at the ligament insertion sites to bone. Other interesting findings include the variation of tensile strains along the ligament substance for all animal species studied.
Unlocking the expressivity of point lights (2012)

Small point lights (e.g., LEDs) are used as indicators in a wide variety of devices today, from digital watches and toasters, to washing machines and desktop computers. Although exceedingly simple in their output - varying light intensity over time - their design space can be rich. Unfortunately, a survey of contemporary uses revealed that the vocabulary of lighting expression in popular use today is small, fairly unimaginative, and generally ambiguous in meaning. In this paper, we work through a structured design process that points the way towards a much richer set of expressive forms and more effective communication for this very simple medium. In this process, we make use of five different data gathering and evaluation components to leverage the knowledge, opinions and expertise of people outside our team. Our work starts by considering what information is typically conveyed in this medium. We go on to consider potential expressive forms -- how information might be conveyed. We iteratively refine and expand these sets, concluding with ideas gathered from a panel of designers. Our final step was to make use of thousands of human judgments, gathered in a crowd-sourced fashion (265 participants), to measure the suitability of different expressive forms for conveying different information content. This results in a set of recommended light behaviors that mobile devices, such as smartphones, could readily employ.
NIST-Sponsored Interlaboratory Comparison of Polystyrene Molecular Mass Distribution Obtained by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry:  Statistical Analysis (2001)

The method of preparation and methods of analysis of a narrow distribution polystyrene of ∼7 ku used in an interlaboratory comparison of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) of synthetic polymers is described. Size exclusion chromatography was used to measure the polystyrene sample variability. Fourier transform infrared spectroscopy and MALDI-TOF-MS were used to analyze end groups on the polymer. The polystyrene was analyzed by MALDI-TOF-MS and classical methods of polymer characterization. The number (Mn) and mass (Mw) average of the molecular mass distribution (MMD) determined by the classical methods (light scattering and NMR) were compared with those obtained by MALDI-TOF-MS. Agreement between classical methods to obtain the moments of the MMD and the MALDI is found to be good overall. However, all the experimental values obtained by MALDI fell below the classical values. A discussion of why these values are lower is included. We discuss the statistical analysis of the data from the interlaboratory comparison conducted by NIST, which includes data from 23 different laboratories. Analysis of variance is used to examine the influences of the independent parameters (laboratory, matrix, instrument manufacturer, instrument mode) on the data. The parameters, laboratory and instrument manufacturer, were determined to have an influence on the MMD, where matrix and instrument mode were found not to have a significant influence.
Hamster cardiomyopathy. A defect in oxidative phosphorylation in the cardiac interfibrillar mitochondria. (1982)

To determine whether or not an oxidative defect exists in hearts of cardiomyopathic (BIO 14.6) hamsters, cardiac tissue and subcellular organelles were studied.Using homogenates of hearts, the sarcolemmal marker, 5'-nucleotidase, was decreased, whereas the lysosomal enzymes, acid phosphatase and N-acetylglucosaminidase, were increased in the cardiomyopathic hearts compared to controls.The mitochondrial enzymes, enoyl-CoA hydratase, P-hydroxyacyl-CoA dehydrogenase, and citrate synthase, were depressed in the cardiomyopathic hearts.The content of coenzyme A was unaltered, but the content of carnitine was depressed in the cardiomyopathic hearts.Just as in normal hamster hearts, two populations of mitochondria were present in the hearts of the cardiomyopathic hamsters.Oxidative phosphorylation b y subsarcolemmal mitochondria was similar in the controls and in the cardiomyopathic hearts.State 3, ADPstimulated respiration was significantly decreased in interfibrillar mitochondria from the cardiomyopathic hearts compared to the same mitochondria from controls.This decrease was seen with both NAD-and FADlinked substrates.Analysis of mitochondrial enzymes did not provide an explanation f o r the depressed oxidation rates.The content of cytochromes cl, c, b, and aa3 was not altered in the cardiomyopathic mitochondria compared to controls.NADH oxidase also was not affected by the cardiomyopathic process.The properties of the mitochondrial inner membrane, possibly involving transport, m a y be responsible f o r the changes in state 3 respiration in interfibrillar mitochondria in the cardiomyopathic hamster heart.W e conclude that a mitochondrial oxidative defect is present in cardiac muscle cells in cardiomyopathic hamsters, but that it is confined wholly to the interfibrillar mitochondria.O u r observations thus reconcile the disparate findings of other investigators.
An effective region-based image retrieval framework (2002)

We present a region-based image retrieval framework that integrates efficient region-based representation in terms of storage and retrieval and effective on-line learning capability. The framework consists of methods for image segmentation and grouping, indexing using modified inverted file, relevance feedback, and continuous learning. By exploiting a vector quantization method, a compact region-based image representation is achieved. Based on this representation, an indexing scheme similar to the inverted file technology is proposed. In addition, it supports relevance feedback based on the vector model with a weighting scheme. A continuous learning strategy is also proposed to enable the system to self improve. Experimental results on a database of 10,000 general-purposed images demonstrate the efficiency and effectiveness of the proposed framework.
On application of virtual fixtures as an aid for telemanipulation and training (2003)

This paper presents a study on the application of virtual fixtures as a control aid for performing telemanipulation or in the training environment. The implementation features both manual and supervisory control modes. It also studies approaches for using virtual fixtures in generating visual and force clues and/or for restricting the motion of the slave using the definition of virtual fixtures. In this preliminary study it was found that the virtual fixtures could: improve the speed and precision of the operator, and reduce the operator's workload and the duration of the training phase for the novice operator.