gebhart/patrepeval huggingface dataset:
Venous Thromboembolism and Cancer: Risks and Outcomes (2003)

Cancer and its treatments are well-recognized risk factors for venous thromboembolism (VTE). Evidence suggests that the absolute risk depends on the tumor type, the stage or extent of the cancer, and treatment with antineoplastic agents. Furthermore, age, surgery, immobilization, and other comorbid features will also influence the overall likelihood of thrombotic complications, as they do in patients without cancer. The role of hereditary thrombophilia in patients with cancer and thrombosis is still unclear, and screening for this condition in cancer patients is not indicated. The most common malignancies associated with thrombosis are those of the breast, colon, and lung, reflecting the prevalence of these malignancies in the general population. When adjusted for disease prevalence, the cancers most strongly associated with thrombotic complications are those of the pancreas, ovary, and brain. Idiopathic thrombosis can be the first manifestation of an occult malignancy. However, intensive screening for cancer in patients with VTE often does not improve survival and is not generally warranted. Independently of the timing of cancer diagnosis (before or after the VTE), the life expectancy of cancer patients with VTE is relatively short, because of both deaths from recurrent VTE and the cancer itself. Patients with cancer and acute VTE who take anticoagulants for an extended period are at increased risk of recurrent VTE and bleeding. A recent randomized trial, the Randomized Comparison of Low Molecular Weight Heparin versus Oral Anticoagulant Therapy for Long-Term Anticoagulation in Cancer Patients with Venous Thromboembolism (CLOT) study, showed that low molecular weight heparin may be a better treatment option for this group of patients. The antineoplastic effects of anticoagulants are being actively investigated with promising preliminary results.
Life and death of transcriptional co-activator p300 (2011)

Transcriptional co-activator p300, which contains an intrinsic histone acetyltransferase activity, is required for an array of important cellular processes. Tight control of p300 function is critical to ensure precise histone acetylation and gene activation. Dysregulation of p300 has been implicated in many types of diseases and numerous studies have examined the functional requirement of p300 to act as a co-activator or as an acetyltransferase for other transcription regulators. Few, however, have tackled how p300 itself is regulated and if posttranslational modification and spatial distribution are means of p300 regulation. In this article, we present a current view on the molecular mechanisms by which the activity and stability of p300 is regulated.
A Time Course of Contusion-Induced Oxidative Stress and Synaptic Proteins in Cortex in a Rat Model of TBI (2008)

An imbalance between oxidants and antioxidants has been postulated to lead to oxidative damage in traumatic brain injury (TBI). Oxidative neurodegeneration is a key mediator of exacerbated morphological responses and deficits in behavioral recoveries. The present study was designed to delineate the early temporal sequence of this imbalance in order to enhance possible antioxidant therapy. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion. At various times post-trauma (3, 6, 12, 24, 48, 72, and 96 h), animals were killed and the cortex analyzed for enzymatic and non-enzymatic oxidative stress markers. Fresh tissues were prepared for biochemical analysis of several antioxidants (glutathione [GSH], glutathione peroxidase [GPx], glutathione reductase [GR], glutathione-S-transferase [GST], and thiobarbituric acid reactive substances [TBARS]). Synaptic markers Synapsin-I, PSD-95, SAP-97 and GAP-43 were analyzed by Western blot with antibodies directed against them. All activity levels were compared to sham-operated animals. Activity of antioxidant enzymes and GSH clearly demonstrate a significant time-dependent increase in oxidative stress. Changes in pre- and post-synaptic proteins (Synapsin-I and PSD-95) occur early (24 h), whereas SAP-97 levels demonstrate a protracted reduction. These results indicate that depletion of antioxidant systems following trauma could adversely affect synaptic function and plasticity. Because of the observed differences in the time-course of various markers, it may be necessary to stagger selective types of anti-oxidant therapy to target specific oxidative components. The initial therapeutic window following TBI appears relatively short since oxidative damage occurs as early as 3 h.
Call path profiling (1992)

Article Free Access Share on Call path profiling Author: Robert J. Hall View Profile Authors Info & Claims ICSE '92: Proceedings of the 14th international conference on Software engineeringJune 1992 Pages 296–306https://doi.org/10.1145/143062.143147Published:01 June 1992Publication History 35citation516DownloadsMetricsTotal Citations35Total Downloads516Last 12 Months37Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
An autologous oral DNA vaccine protects against murine melanoma (2000)

We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide epitopes gp100(25-33) and TRP-2(181-188). These epitopes contain dominant anchor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectively. The DNA vaccine was delivered by oral gavage by using an attenuated strain of Salmonella typhimurium as carrier. Tumor-protective immunity was mediated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression after a lethal challenge with B16G3. 26 murine melanoma cells. Importantly, the protective immunity induced by this autologous DNA vaccine against murine melanoma cells was at least equal to that achieved through xenoimmunization with the human gp100(25-33) peptide, which differs in its three NH(2)-terminal amino acid residues from its murine counterpart and was previously reported to be clearly superior to an autologous vaccine in inducing protective immunity. The presence of ubiquitin upstream of the minigene proved to be essential for achieving this tumor-protective immunity, suggesting that effective antigen processing and presentation may make it possible to break peripheral T cell tolerance to a self-antigen. This vaccine design might prove useful for future rational designs of other recombinant DNA vaccines targeting tissue differentiation antigens expressed by tumors.
Examination of living and fixed gametes and early embryos stained with supravital fluorochromes (Hoechst 33342 and 3,3′‐dihexyloxacarbocyanine iodide) (1986)

Abstract We have examined living and fixed gametes and early embryos of surf clams, sea urchins, and hamsters stained with the supravital dyes Hoechst 33342 for DNA and 3,3′‐dihexyloxacarbocyanine iodide (DIOC 6 ) for mitochondria and endoplasmic reticulum. Hoechst staining (10 μM) was confined exclusively to egg and sperm chromatin and, in living marine specimens, did not interfere with sperm motility, fertilization, or nuclear activity during meiosis or early embryogenesis. Although Hoechst staining did not appear to affect the motility of hamster sperm, only zonae‐free eggs inseminated. Because chromatin retained Hoechst 33342 stain during fertilization, the paternally and maternally derived chromosomes of living and fixed preparations fluoresced and their number, organization, and location within the zygote cytoplasm could be determined. Hence, polyspermy and other nuclear abnormalities were amenable to examination in these stained preparations. DIOC 6 staining (8.7 μM) was restricted primarily to the mitochondria of spermatozoa. Eggs stained with DIOC 6 (0.87 to 8.7 μM) were brightly fluorescent because of their size and the presence of large numbers of mitochondria and other DIOC 6 ‐positive organelles. Sea urchin and surf clam sperm stained with DIOC 6 fertilized unstained eggs and the location of the incorporated sperm mitochondrion up to first cleavage was followed. Although hamster sperm stained with DIOC 6 were less motile than unstained sperm, they were capable of inseminating only zonae‐free eggs. These observations demonstrate that staining with supravital fluorochromes provides a rapid and useful method to analyze macromolecular and organelle changes in a variety of living and fixed gametes and embryos.
Akt Enhances Mdm2-mediated Ubiquitination and Degradation of p53 (2002)

p53 plays a key role in DNA damage-induced apoptosis. Recent studies have reported that the phosphatidylinositol 3-OH-kinase-Akt pathway inhibits p53-mediated transcription and apoptosis, although the underlying mechanisms have yet to be determined. Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good substrate for Akt. In this study, we find that expression of Akt reduces the protein levels of p53, at least in part by enhancing the degradation of p53. Both Akt expression and serum treatment induced phosphorylation of Mdm2 at Ser186. Akt-mediated phosphorylation of Mdm2 at Ser186 had little effect on the subcellular localization of Mdm2. However, both Akt expression and serum treatment increased Mdm2 ubiquitination of p53. The serum-induced increase in p53 ubiquitination was blocked by LY294002, a phosphatidylinositol 3-OH-kinase inhibitor. Moreover, when Ser186 was replaced by Ala, Mdm2 became resistant to Akt enhancement of p53 ubiquitination and degradation. Collectively, these results suggest that Akt enhances the ubiquitination-promoting function of Mdm2 by phosphorylation of Ser186, which results in reduction of p53 protein. This study may shed light on the mechanisms by which Akt promotes survival, proliferation, and tumorigenesis.
Drug treatments for metastasis of the Lewis lung carcinoma: lack of correlation between inhibition of lung metastasis and survival. (1989)

The abilities of the Eli Lilly compounds LY150310, LY189332, and LY135305 to inhibit spontaneous metastasis and to increase animal survival were evaluated. These compounds represent widely varied structures and were evaluated because they have been found to inhibit thromboxane synthetase, cyclooxygenase, and thrombin activation, respectively. These biochemical processes have been proposed in the literature as targets for antimetastatic drugs. The purpose of this investigation was twofold: (a) to compare the antimetastatic activities of the Eli Lilly compounds to those of the reference antimetastatic compounds nafazatrom and RA233, and (b) to examine the correlation between inhibition of spontaneous lung metastasis and survival. Spontaneous metastasis of the Lewis lung carcinoma was used to evaluate the antimetastatic activity of the compounds. In this model 5 x 10(5) tumor cells were implanted into the gastrocnemius muscle, the primary tumor was resected on Day 14, and metastatic lung lesions were counted on Day 25. Compounds were administered every 12 h on Days 5 through 19. Nafazatrom, LY150310, LY189332, and LY135305 were found to inhibit spontaneous lung metastasis in a dose-dependent manner. The ED50 values for the respective inhibitions with these compounds were 50, 0.5, 2, and 0.35 mg/kg/day; the respective therapeutic indexes (LD50/ED50) were 7, 180, 255, and 511. To evaluate the effect of nafazatrom, LY150310, LY189332, and LY135305 on animal survival, the compounds were given at maximally antimetastatic doses of 200, 60, 20, and 6 mg/kg/day, respectively. Two dosing schedules were used: (a) on Days 5 through 19 and (b) on Day 5 until death. Neither the median survival times nor the numbers of long-term survivors were significantly changed with any of the compounds at any dosing schedule. RA233, given to a maximally tolerated dose of 200 mg/kg/day on Day 5 until death, did not inhibit lung metastasis and did not increase median survival time. Postmortem examination of animals dosed with nafazatrom, LY150310, LY189332, and LY135305 showed complete inhibition in lung lesions and the appearance of lesions in the liver, kidney, spleen, and brain. The results of this investigation show that the effect a compound has on the number of metastatic lesions in a target organ may not be predictive of its effect on survival. To successfully translate laboratory data into the clinic, survival should be considered as a predictor of a compound's potential clinical utility.
Paired-Flash Identification of Rod and Cone Dysfunction in the Diabetic Rat (2004)

Retinal neural dysfunction was observed as early as 2 days after STZ injection. These acute changes reflect either STZ toxicity or hyperglycemia as a result of pancreatic compromise. Consistent loss over the 12 weeks of the cone response and OPs suggests a vulnerability of the inner retina to STZ-related effects. The 12-week losses in function of retinal neurons are consistent with a generalized diabetic neuropathy, since impaired function developed simultaneously in both inner and outer retinal neurons.
High-Sensitivity Atomic Magnetometer Unaffected by Spin-Exchange Relaxation (2002)

Alkali-metal magnetometers compete with SQUID detectors as the most sensitive magnetic field sensors. Their sensitivity is limited by relaxation due to spin-exchange collisions. We demonstrate a K magnetometer in which spin-exchange relaxation is completely eliminated by operating at high K density and low magnetic field. Direct measurements of the signal-to-noise ratio give a magnetometer sensitivity of 10 fT Hz(-1/2), limited by magnetic noise produced by Johnson currents in the magnetic shields. We extend a previous theoretical analysis of spin exchange in low magnetic fields to arbitrary spin polarizations and estimate the shot-noise limit of the magnetometer to be 2x10(-18) T Hz(-1/2).
Genome-Wide Off-Target Analysis in CRISPR-Cas9 Modified Mice and Their Offspring (2019)

The emergence of the CRISPR-Cas9 system has triggered a technical revolution in mammalian genome editing. Compared to traditional gene-targeting strategies, CRISPR-Cas9 technology offers a more efficient and cost-effective approach for generating genetically modified animal models. However, off-target cleavage in CRISPR-mediated genome editing is a major concern in the analysis of phenotypes as well as the selection of therapeutic targets. Here, we analyzed whole-genome sequencing (WGS) data from two knock-out (KO) mouse strains generated by using the CRISPR-Cas9 system targeting the <i>Mmd</i> and <i>Paqr8</i> loci. A total of nine individuals were sequenced including two parents, four F1 offspring and three uninjected control mice. Using GATK and bcftools software, we identified two off-target events in the founder mice. The two CRISPR-Cas9-induced off-target events were predictable using Cas-OFFinder and were not passed on to the offspring that we investigated. In addition, our results indicated that the number of CRISPR-Cas9-induced mutations was not statistically distinguishable from the background <i>de novo</i> mutations (DNMs).
Characterization of a spontaneous murine B cell leukemia (BCL1). I. Cell surface expression of IgM, IgD, Ia, and FcR. (1979)

The surface marker expression of a spontaneous B lymphocyte leukemia discovered in a BALB/c mouse (BCL1) was examined and found to include a subset of markers known to occur on normal B lymphocytes. The tumor cells bore surface Ig that included both mu- and delta-chains associated with the lambda light chain. Alloantigens coded for within the murine MHC, including H-2D, H-2K, and I-region products, were identified on the tumor cells. Although normal B lymphocytes are thought to express products coded for within both the I-A and I-E subregions, the BCL1 expressed only normal amounts of I-E subregion products. In addition, the H-2 and Ia antigens revealed by 2-dimensional gel electrophoresis exhibited an abnormal pattern of post-translational modifications. The Fc, but not the complement-receptor, was present on the surface of tumor cells. The presence of IgD, Ia antigens, and the responsiveness to lipopolysaccharide (see subsequent paper) have led us to postulate that the BCL1 tumor represents a later differentiative stage than murine B lymphocyte tumors previously described.
New star coupler compatible with single multimode-fibre data links (1976)

A star coupler for optical data links for use with a single multimode fibre, as opposed to fibre bundles, was realised in the form of a multiport directional coupler assembled from bicorical tapers of multimode fibres. The insertion loss above furcation loss of the 4-paired-port coupler was measured to be 2.8 dB.
A framework for flow-based accounting on the Internet (2002)

The authors describe steps toward an accounting mechanism to attribute Internet resource consumption based on service quality. Their objective is not to describe a complete accounting and billing system. Rather they advocate taking advantage of existing Internet instrumentation to implement incremental improvements in the short to medium term. Experience from these improvements can allow more educated progress towards a comprehensive Internet accounting system.
Differentiation of Benign and Malignant Pulmonary Nodules by Growth Rate (1962)

Solitary pulmonary nodules have been analyzed by many investigators (11, 13, 15, 16, 17, 31, 33, 38, 43) for signs indicative of their etiology, the main effort having been directed toward separation of benign and malignant lesions. Of all the signs mentioned, including size, shape, density, sharpness of margin, umbilication, satellite nodules, cavitation, densities extending into the hilus and/or pleura, growth, and calcification, only the last has been considered to be a reliable aid in differentiation. The presence of any calcification in a pulmonary lesion makes malignancy extremely unlikely, although it is recognized that minute central calcification can on rare occasions be found in malignant lesions. Ring-shaped, laminated, and large central "popcorn" calcifications are reliable signs of benignity (16, 31). In general, the appearance of a nodule in a lung which was previously normal or enlargement of a pulmonary nodule, with the reservation that there are some exceptions, is thought by most to indicate a malignant lesion. Because of the difficulty in differentiating benign from malignant nodules, the general attitude in the last few years, particularly since about 1945, has been to recommend the immediate removal of all solitary pulmonary nodules except those in which the presence of calcification indicates their benign nature. Few objections have been raised against this procedure. One of those who protests is Garland (13) who advised: "Don't be like Lady Macbeth. Don't say 'Out, damned spot!' and I think you will diagnose most of these nodules correctly. " The concept of exponential growth of cancer at a constant rate, advanced by Mottram in 1935 (29) and later by Collins et al. in 1956 (5), has received support in the work of several independent investigators (1, 2, 10, 21, 22, 25, 34, 41, 42). Collins collected a series of 177 cases of malignant pulmonary nodules with serial chest films showing the growth of neoplastic nodules. The nodules were measured and growth rate was expressed as "doubling time." Values ranged from 7 to 465 days (5–9). Enlargement of non-neoplastic. nodules also may occur, but the mechanisms are not the same as for neoplasms and would not be expected to result necessarily in exponential growth at a constant rate. Although granulomas, pneumonitis, abscesses, infarcts, hematomas, fluid collections, etc., may enlarge, they do not do so by cell division. Nevertheless, observation of change (or lack of change) in size may demonstrate that the pattern of growth is not that of a malignant tumor. This may therefore be a useful diagnostic test. If differences could be found to exist between the rate of tumor growth and the rate of enlargement of benign lesions, then a useful diagnostic tool would become available to add to the few radiographic and clinical signs for differential diagnosis.
Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. (2000)

The length of the polymorphic CAG trinucleotide repeat in the polyglutamine region of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Because increased androgenic activity has been linked to prostate cancer and because an ethnic variation exists in the CAG repeat length, this polymorphism has been suggested to explain part of the substantial racial difference in prostate cancer risk. We conducted a population-based case-control study in China to investigate whether CAG and other polymorphisms of the AR gene are associated with clinically significant prostate cancer in this low-risk population. Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene. Relative to western men, our study subjects had a longer CAG repeat length, with a median of 23 and only 10% of the subjects having a CAG repeat length shorter than 20. Men with a CAG repeat length shorter than 23 (median length) had a 65% increased risk of prostate cancer (odds ratio, 1.65; 95% confidence interval, 1.14-2.39), compared with men with a CAG repeat length of 23 or longer. For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions. More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats. Our study not only confirms that Chinese men do have a longer CAG repeat length than western men but also represents the first population-based study to show that even in a very low-risk population, a shorter CAG repeat length confers a higher risk of clinically significant prostate cancer. These results imply that CAG repeat length can potentially serve as a useful marker to identify a subset of individuals at higher risk of developing clinically significant prostate cancer. Larger studies are needed to evaluate the combined effect of CAG and GGN repeats. Because of the significance of AR in prostate cancer, investigation of factors that interact with the polyglutamine region of the AR gene to alter AR function and modulate prostate cancer risk is an important area for future research.
Dendrimers and magnetic resonance imaging (2007)

The multivalent character of dendrimers has positioned these well-defined, highly branched macromolecules at the forefront in the development of new contrast agents for biomedical magnetic resonance imaging (MRI). By modifying the periphery of the dendrimer with gadolinium(III) chelates, the relaxivity of the resulting MRI contrast agent is increased considerably, compared to low molecular weight Gd(III) chelates. The monodisperse character of dendrimers creates a unique opportunity to introduce dendritic MRI contrast agents into clinics. In addition, a prolonged vascular retention time is obtained due to the larger size of the dendritic molecules. By using dendrimers as multivalent scaffolds carrying multiple ligands, the interaction between ligand and marker can be enhanced through multivalent interactions. Current research focuses on the combination of multivalent targeting and enhanced relaxivity. This paper describes the application of dendrimers in biomedical MRI.