gebhart/patrepeval huggingface dataset:
Final Pathology Findings After Immediate or Delayed Surgery in Patients with Cytologically Benign or Follicular Thyroid Nodules (2010)

Our criteria for surgical indication of nodules diagnosed as cytological benign or follicular tumors were considered appropriate. Ultrasonographic evaluation is an important and useful basis for therapeutic decision making in choosing either immediate surgery or observation for cytologically diagnosed benign or follicular tumors.
Feedback Mechanisms Regulate Ets Variant 2 (Etv2) Gene Expression and Hematoendothelial Lineages (2015)

Etv2 is an essential transcriptional regulator of hematoendothelial lineages during embryogenesis. Although Etv2 downstream targets have been identified, little is known regarding the upstream transcriptional regulation of Etv2 gene expression. In this study, we established a novel methodology that utilizes the differentiating ES cell and embryoid body system to define the modules and enhancers embedded within the Etv2 promoter. Using this system, we defined an autoactivating role for Etv2 that is mediated by two adjacent Ets motifs in the proximal promoter. In addition, we defined the role of VEGF/Flk1-Calcineurin-NFAT signaling cascade in the transcriptional regulation of Etv2. Furthermore, we defined an Etv2-Flt1-Flk1 cascade that serves as a negative feedback mechanism to regulate Etv2 gene expression. To complement and extend these studies, we demonstrated that the Flt1 null embryonic phenotype was partially rescued in the Etv2 conditional knockout background. In summary, these studies define upstream and downstream networks that serve as a transcriptional rheostat to regulate Etv2 gene expression.
Novel Terphenyls as Selective Cyclooxygenase-2 Inhibitors and Orally Active Anti-inflammatory Agents (1996)

A novel series of terphenyl methyl sulfones and sulfonamides have been shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely advantageous for both in vitro COX-2 potency and selectivity as well as in vivo activity. Several noticeable examples in the 1,2-diaryl-4,5-difluorobenzenesulfonamide series are 21a-c,k,l,n (COX-2, IC50 = 0.002-0.004 microM), in which all have in vitro COX-1/COX-2 selectivity > 1000. In addition, sulfonamides 21a,b,d,g,j,m,n,q were shown to have greatly enhanced oral activity with more than 90% inhibition of prostaglandin E2 production in the air pouch model of inflammation. Furthermore, sulfonamide 21b was found to be very active in the rat adjuvant-induced arthritis model (ED50 = 0.05 mg/kg) and carrageenan-induced hyperalgesia assay (ED50 = 38.7 mg/kg) with no indication of gastrointestinal toxicity in rats at doses as high as 200 mg/kg.
Two-dimensional arrangement of chromophores in J aggregates of long-chain merocyanines and its effect on energy transfer in monolayer systems (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTwo-dimensional arrangement of chromophores in J aggregates of long-chain merocyanines and its effect on energy transfer in monolayer systemsHiroo Nakahara, Kiyoshige Fukuda, Dietmar Moebius, and Hans KuhnCite this: J. Phys. Chem. 1986, 90, 23, 6144–6148Publication Date (Print):November 1, 1986Publication History Published online1 May 2002Published inissue 1 November 1986https://pubs.acs.org/doi/10.1021/j100281a019https://doi.org/10.1021/j100281a019research-articleACS PublicationsRequest reuse permissionsArticle Views503Altmetric-Citations152LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Ultrastructural distribution of fibronectin in normal and fibrotic human lung. (1985)

We studied the distribution of fibronectin in normal and fibrotic adult human lung and normal hamster lung using affinity-purified antifibronectin Fab'-horseradish peroxidase conjugates. In normal lung, fibronectin staining was present in alveolar capillary and epithelial basal lamina and associated with interstitial collagen fibers. In airway and larger vessels, fibronectin staining was associated with the basal lamina of smooth muscles. In contrast to the relative paucity of staining in normal lung, the alveolar basal lamina of fibrotic lung stained intensely for fibronectin. In addition, there was strong, periodic (approximately 600 A) staining of native collagen fibers for fibronectin. We conclude that fibronectin antigenicity is present in the alveolar epithelial and capillary endothelial basal lamina of normal human and hamster lung. The marked alterations in the apparent amounts and distribution of fibronectin in fibrotic human lung suggest its involvement in the cellular events accompanying human lung fibrosis.
Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation (1992)

1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated. 2. Low doses (1g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5g resulted in a mean peak after 1h of 795 (SD 104) mumol/l in three subjects weighing 76-87 kg. Repeated dosing with 5g every 2h sustained the plasma concentration at around 1000 mumol/l. A single 5g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak. 3. Supplementation with 5g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%. 4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 x 5g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.(ABSTRACT TRUNCATED AT 250 WORDS)
Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma. (1999)

Beta-catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both E-cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless pathway. Stabilization of beta-catenin followed by nuclear translocation and subsequent T-cell factor/lymphoid-enhancing factor-mediated transcriptional activation has been proposed as an important step in oncogenesis. Stabilization may occur through activating mutations in exon-3 at the phosphorylation sites for ubiquitination and degradation of beta-catenin. Immunohistochemical subcellular localization of beta-catenin and mutational analysis of exon-3 of the beta-catenin gene by single-strand conformational polymorphism followed by DNA sequencing was performed on 37 samples from 31 patients with anaplastic thyroid carcinoma. Immunofluorescent staining showed nuclear localization in 15 (42%) of the 36 samples examined. Nucleotide sequencing of mobility shifts detected by single-strand conformational polymorphism revealed somatic alterations in 19 (61%) of the 31 patients analyzed. We conclude that mutations in beta-catenin are common in anaplastic thyroid cancer and that they may activate transcription, as illustrated by frequent nuclear localization of the protein. These findings support the idea that beta-catenin acts as an oncogene and contributes to the highly aggressive behavior of this tumor.
A survey and comparison of wormhole routing techniques in a mesh networks (1997)

The growing demand for high processing power in various scientific and engineering applications has made multiprocessing architectures increasingly popular. These multiprocessing systems consist of processing elements or nodes which are connected together by interconnection networks in various topologies. One of the design methodologies used for parallel machines has fed to the development of distributed memory message-passing concurrent computers, commonly known as multicomputers. They consist of many processing nodes that interact by sending messages (containing both data and synchronization information) over a communication link, between nodes. Thus, efficient communication in multicomputers is one of the important research areas in parallel computing today, and it depends on the underlying scheme for routing. For this reason it is essential to know which routing techniques are suitable and practical. Although an extremely wide number of routing algorithms have been proposed and implemented in hardware and software, it is difficult for the designer of a multicomputer to choose the best routing algorithm given a particular architectural configuration. In an attempt to overcome this difficulty, we present a survey and comparison of wormhole routing techniques in mesh interconnection networks. The mesh topology is important because of its scalability. Moreover, it has already been implemented in many commercial multicomputers.
The Discovery of Novel Human Androgen Receptor Antagonist Chemotypes Using a Combined Pharmacophore Screening Procedure (2013)

Unraveling the mechanisms involved in castration- and therapy-resistant prostate cancer has led to a renewed interest in androgen receptor (AR)-targeted therapeutics. Anti-androgens that block the activity of the AR therefore remain a valid therapeutic option. However, they must be more effective than, or display a distinct mechanism of action or binding mode from those of bicalutamide and hydroxyflutamide, which are currently in clinical use. For that reason, the second-generation anti-androgen MDV3100 was developed. MDV3100, however, shares its 4-cyano-3-(trifluoromethyl)phenyl group with bicalutamide and hydroxyflutamide required for binding to the AR. In this work, we used a combined strategy to find new antagonist structures distinct from the 4-cyano-3-(trifluoromethyl)phenyl group to avoid cross-resistance for these compounds and to find structures without agonist activity on mutant ARs (AR W741C and AR T877A). We found two novel chemotypes with AR-antagonistic activity (IC(50): 3-6 μM) by virtual screening and confirmed their biological activity in an androgen-responsive reporter assay. The design of our computational approach was validated by the observation of strongly decreased or absence of agonistic activity on the two mutant ARs. Further structural derivatization to optimize the potency of these compounds can render these chemotypes into very promising, alternative AR antagonists for prostate cancer therapy.
Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells (1998)

Negative as well as positive co-stimulation appears to play an important role in controlling T cell activation. CTLA-4 has been proposed to negatively regulate T cell responses. CTLA-4-deficient mice develop a lymphoproliferative disorder, initiated by the activation and expansion of CD4+ T cells. To assess the function of CTLA-4 on CD8+ T cells, CTLA-4(-/-) animals were crossed to an MHC class I-restricted 2C TCR transgenic mouse line. We demonstrate that although the primary T cell responses were similar, the CTLA-4-deficient 2C TCR+ CD8+ T cells displayed a greater proliferative response upon secondary stimulation than the 2C TCR+ CD8+ T cells from CTLA-4 wild-type mice. These results suggest that CTLA-4 regulates antigen-specific memory CD8+ T cell responses.
Accelerating Cancer Therapy Development: The Importance of Combination Strategies and Collaboration. Summary of an Institute of Medicine Workshop (2012)

Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies.
Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells (1997)

The function of cell surface-associated insulin-like growth factor-binding proteins (IGFBPs) is controversial. Both inhibition and facilitation of IGF action as well as IGF-independent effects have been reported. We examined the influence of endogenous cell surface-associated IGFBPs on IGF-I receptor (IGF-IR) function in Ishikawa endometrial cancer cells by comparing the effects of IGF-I and its truncated analog des-(1–3)-IGF-I on several components of the IGF-IR signal transduction pathway in the absence of significant amounts of soluble IGFBPs. IGF-I and des-(1–3)-IGF-I are known to have similar affinities for IGF-IR, although the affinity of des-(1–3)-IGF-I for IGFBPs is greatly reduced. Here we show that the two ligands were equipotent not only in IGF-IR binding but also in receptor activation in NIH 3T3 cells overexpressing IGF-IR and possessing a relatively small number of cell surface-associated IGFBPs. In contrast, des-(1–3)-IGF-I manifested a remarkably higher potency as compared with IGF-I in inducing short and middle term cellular responses in IGF-IR-transfected Ishikawa endometrial cancer cells possessing a high number of both the receptor and the cell membrane-bound IGFBP-3. Thus, this difference in the effects of IGF-I and des-(1–3)-IGF-I can be attributed to the attenuation of IGF-I-mediated IGF-IR signaling by membrane-bound IGFBP-3.
Teaching Vaccine Safety Communication to Medical Students and Health Professionals (2015)

Not only the general public, but also those studying to become health professionals, are struggling to keep up with a growing body of evidence and increasingly complex information about the many different types of vaccines available to date. At the same time, a number of increasingly complex subjects of study are competing for their attention during undergraduate and graduate education. In many medical school curricula in German-speaking countries, the subject of vaccines has been entirely omitted, or is regarded a minor subtopic. During the studies, most medical school curricula in German-speaking countries do not offer obligatory courses and/ or hands-on training vaccinology in vaccination. In Germany, private pediatricians administer the majority of immunizations. Even during postgraduate training programs in pediatrics, which are largely hospital-based, vaccinations are rarely a topic, and vaccinology remains a "hobby" and a "field without lobby" lacking specific certification requirements. Studies of acceptance of vaccines among health professionals and medical students have shown that many may still have their own doubts and uncertainties about vaccines revealing a number of unanswered questions during their studies and postgraduate training.
Influence of increased aspartate availability on lysine formation by a recombinant strain of Corynebacterium glutamicum and utilization of fumarate (1989)

Aspartate availability was increased in Corynebacterium glutamicum strains to assess its influence on lysine production. Upon addition of fumarate to a strain with a feedback-resistant aspartate kinase, the lysine yield increased from 20 to 30 mM. This increase was accompanied by the excretion of malate and succinate. In this strain, fumaric acid was converted to aspartate by fumarate hydratase, malate dehydrogenase, and aspartate amino transferase activity. To achieve the direct conversion of fumarate to aspartate, shuttle vectors containing the aspA+ (aspartase) gene of Escherichia coli were constructed. These constructions were introduced into C. glutamicum, which was originally devoid of the enzyme aspartase. This resulted in an aspartase activity of 0.3 U/mg (70% of the aspartase activity in E. coli) with plasmid pZ1-9 and an activity of up to 1.05 U/mg with plasmid pCE1 delta. In aspA+-expressing strains, lysine excretion was further increased by 20%. Additionally, in strains harboring pCE1 delta, up to 27 mM aspartate was excreted. This indicates that undetermined limitations in the sequence of reactions from aspartate to lysine exist in C. glutamicum.
pH dependence, substrate specificity and inhibition of human kynurenine aminotransferase I (2004)

Human kynurenine aminotransferase I/glutamine transaminase K (hKAT-I) is an important multifunctional enzyme. This study systematically studies the substrates of hKAT-I and reassesses the effects of pH, Tris, amino acids and alpha-keto acids on the activity of the enzyme. The experiments were comprised of functional expression of the hKAT-I in an insect cell/baculovirus expression system, purification of its recombinant protein, and functional characterization of the purified enzyme. This study demonstrates that hKAT-I can catalyze kynurenine to kynurenic acid under physiological pH conditions, indicates indo-3-pyruvate and cysteine as efficient inhibitors for hKAT-I, and also provides biochemical information about the substrate specificity and cosubstrate inhibition of the enzyme. hKAT-I is inhibited by Tris under physiological pH conditions, which explains why it has been concluded that the enzyme could not efficiently catalyze kynurenine transamination. Our findings provide a biochemical basis towards understanding the overall physiological role of hKAT-I in vivo and insight into controlling the levels of endogenous kynurenic acid through modulation of the enzyme in the human brain.
Computer‐aided diagnoses: Automatic detection of lung nodules (1998)

This work describes a computational scheme for automatic detection of suspected lung nodules in a chest radiograph. A knowledge-based system extracts the lung masks over which we will apply the nodule detection process. First we obtain the normalized cross-correlation image. Next we detect suspicious regions by assuming a threshold. We examine the suspicious regions using a variable threshold which results in the growth of the suspicious areas and an increase in false positives. We reduce the large number of false positives by applying the facet model to the suspicious regions of the image. An algorithmic classification process gives a confidence factor that a suspicious region is a nodule. Five chest images containing 30 known nodules were used as a training set. We evaluated the system by analyzing 30 chest images with 40 confirmed nodules of varying contrast and size located in various parts of the lungs. The system detected 100% of the nodules with a mean of six false positives per image. The accuracy and specificity were 96%.
Antibodies against synthetic peptides of herpes simplex virus type 1 glycoprotein D and their capability to neutralize viral infectivity in vitro (1988)

Peptides corresponding to residues 1-13, 9-21, 18-30, 82-93, 137-150, 181-197, 232-243, 235-243, 267-281, 271-281 and 302-315 of glycoprotein D of herpes simplex virus type 1 (HSV-1) were chemically synthesized. These peptides were coupled to carrier proteins, and the resulting conjugates were used to immunize rabbits. An enzyme-linked immunosorbent assay was used to determine antipeptide antibody titers in serum collected after immunization. All peptides appeared to be immunogenic in rabbits. Western immunoblot analysis with detergent extracts of HSV-1-infected Vero cells showed that antibodies against each of the peptides were able to react with the parent glycoprotein under denaturing conditions. Antisera against peptides 1-13, 9-21, and 18-30 neutralized HSV-1 infectivity in vitro, peptide 9-21 being the most successful in this respect. Immunization with a mixture of peptides 9-21 and 267-281 yielded antisera which reacted strongly with glycoprotein gD in Western blot analysis and showed a more solid virus-neutralizing activity in vitro.
Transformation of bovine peripheral blood lymphocytes in the perinatal period. (1985)

Transformation of apparently healthy bovine lymphocytes with phytohemagglutitin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) from peripheral blood in the perinatal period was observed. In multiparous dairy cows, lymphocyte incorporation of 3H-thymidine (3H-TdR) decreased twice within 40 days after calving: the first one occurred within 10 days, and the second one was seen around 30 days after calving, respectively. This trend of decreasing was almost same in the transformation with PHA, ConA and PWM, respectively. On the other hand, the marked decreasing was seen once around 20 days after parturition in primiparous cows.