gebhart/patrepeval huggingface dataset:
Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia (1995)

We have studied the role of the hypoxia-inducible angiogenic growth factor vascular endothelial growth factor (VEGF) in the induction and control of vessel growth in the developing retina of rats and cats, using in situ hybridization techniques. VEGF is expressed successively in two layers of neural retina, the innermost (axon) layer and the inner nuclear layer (INL). In the axon layer, VEGF is expressed transiently by astrocytes as they spread across the layer, closely preceding the formation of superficial vessels. In the INL, VEGF is expressed transiently by somas at the middle of the layer (presumably Müller cells), closely preceding the formation of the deep layer of retinal vessels. We propose that hypoxia caused by the onset of neuronal activity is detected by strategically located populations of neuroglia, first astrocytes, then Müller cells. In response they secrete VEGF, inducing formation of the superficial and deep layers of retinal vessels, respectively. As the vessels become patent, they relieve the hypoxic stimulus, so vessel formation is matched to oxygen demand. This hypothesis was tested experimentally in three ways. Expression of the high affinity flk-1 receptor for VEGF was demonstrated in newly formed retinal vessels, confirming that the secreted VEGF acts on the vessels, in a paracrine fashion. Direct hypoxic regulation of VEGF expression by macroglia was demonstrated in primary cultures of astrocytes and in cells of a glioma line. Hypoxic regulation of VEGF expression in the intact developing retina was demonstrated by showing that oxygen-enriched atmospheres that inhibit vessel formation also suppress endogenous VEGF production.
Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype (2008)

Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein expression was assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2 expression was observed in 13.4 and 5.9% of all breast cancer, respectively. Their expression was strongly associated with high histological grade, lack of steroid hormone receptor positivity (ER and PR), and expression of basal markers (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant association between CAV1 and CAV2 expression and basal-like phenotype. On univariate analysis only CAV2 had a prognostic impact on breast cancer-specific survival; however, this was not independent from other traditional markers on multivariate analysis. Our results demonstrate that both CAV1 and CAV2 are associated with basal-like phenotype. Further studies are warranted to determine whether they play an oncogenic role in basal-like/triple-negative breast cancer development or are just surrogate markers for this subgroup.
Self-Recovering Equalization and Carrier Tracking in Two-Dimensional Data Communication Systems (1980)

Conventional equalization and carrier recovery algorithms for minimizing mean-square error in digital communication systems generally require an initial training period during which a known data sequence is transmitted and properly synchronized at the receiver. This paper solves the general problem of adaptive channel equalization without resorting to a known training sequence or to conditions of limited distortion. The criterion for equalizer adaptation is the minimization of a new class of nonconvex cost functions which are shown to characterize intersymbol interference independently of carrier phase and of the data symbol constellation used in the transmission system. Equalizer convergence does not require carrier recovery, so that carrier phase tracking can be carried out at the equalizer output in a decision-directed mode. The convergence properties of the self-recovering algorithms are analyzed mathematically and confirmed by computer simulation.
Mapping the Hyaluronan-binding Site on the Link Module from Human Tumor Necrosis Factor-stimulated Gene-6 by Site-directed Mutagenesis (2001)

Link modules are hyaluronan-binding domains found in extracellular proteins involved in matrix assembly, development, and immune cell migration. Previously we have expressed the Link module from the inflammation-associated protein tumor necrosis factor-stimulated gene-6 (TSG-6) and determined its tertiary structure in solution. Here we generated 21 Link module mutants, and these were analyzed by nuclear magnetic resonance spectroscopy and a hyaluronan-binding assay. The individual mutation of five amino acids, which form a cluster on one face of the Link module, caused large reductions in functional activity but did not affect the Link module fold. This ligand-binding site in TSG-6 is similar to that determined previously for the hyaluronan receptor, CD44, suggesting that the location of the interaction surfaces may also be conserved in other Link module-containing proteins. Analysis of the sequences of TSG-6 and CD44 indicates that the molecular details of their association with hyaluronan are likely to be significantly different. This comparison identifies key sequence positions that may be important in mediating hyaluronan binding, across the Link module superfamily. The use of multiple sequence alignment and molecular modeling allowed the prediction of functional residues in link protein, and this approach can be extended to all members of the superfamily.
MicroRNA expression in lymphoma (2007)

MicroRNAs are a recently discovered class of short (approximately 22 nucleotide) naturally occurring RNA molecules that negatively regulate gene expression post-transcriptionally. There has been an explosion of interest in the microRNA field as these molecules have been found to play key roles in a wide range of biological processes and to be aberrantly expressed in many types of cancer, including haematological malignancies. Cancer-associated microRNAs can act as both tumour suppressor molecules (e.g., miR-15a and miR-16-1) and have oncogenic properties (e.g., miR-155 and miR-17-92 cluster). In this review the authors discuss the rapidly accumulating evidence for the central role that microRNAs play in both haematopoiesis and haematological malignancy, in particular focusing on their role in lymphoma.
The Ciliopathies: An Emerging Class of Human Genetic Disorders (2006)

Cilia and flagella are ancient, evolutionarily conserved organelles that project from cell surfaces to perform diverse biological roles, including whole-cell locomotion; movement of fluid; chemo-, mechano-, and photosensation; and sexual reproduction. Consistent with their stringent evolutionary conservation, defects in cilia are associated with a range of human diseases, such as primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration. Recent evidence indicates that ciliary defects can lead to a broader set of developmental and adult phenotypes, with mutations in ciliary proteins now associated with nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome. The molecular data linking seemingly unrelated clinical entities are beginning to highlight a common theme, where defects in ciliary structure and function can lead to a predictable phenotypic pattern that has potentially predictive and therapeutic value.
Reactivity of Non-Primate Growth Hormones and Prolactins with Human Growth Hormone Receptors on Cultured Human Lymphocytes (1977)

Ovine placental lactogen is as reactive as human growth hormone with the human growth hormone receptor of cultured human (IM-9) lymphocytes, which confirms the findings of Carr and Friesen with receptors of human liver. We now also show that bovine and ovine growth hormones and ovine prolactin have reactivity for the human growth hormone receptor on IM-9 lymphocytes that is of the same order of magnitude (0.03%) as that previously reported for human placental lactogen. The binding studies predict that these non-primate hormones will have biological effects on skeletal growth in primates, either as agonists or antagonists. Previous studies have shown that when IM-9 lymphocytes are exposed to human growth hormone for 18 h at 37 C, there is a time and concentration dependent loss of human growth hormone receptors, and the magnitude of the loss of receptors after preincubation for 18 h at 37 C is greater than the average occupancy of receptors under steady state conditions for 90 min at 30 C. In the present study we show that human and ovine placental lactogens, ovine prolactin, and bovine and ovine growth hormones also produce this effect on the human growth hormone receptor. Since the cellular process by which a hormone induces loss of its own receptors appears to require binding of the hormone to its receptor as well as one or more subsequent steps in hormone action, it is likely that all of the preparations that induce receptor loss will be shown to have some agonist activity of human growth hormone in promoting skeletal growth in primates. Further, these studies extend the interrelationships between primate and non-primate pituitary and placental hormones from what has been suggested previously from biological and structural studies.
Mechanisms for the removal of benzyl protecting groups in synthetic peptides by trifluoromethanesulfonic acid-trifluoroacetic acid-dimethyl sulfide (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanisms for the removal of benzyl protecting groups in synthetic peptides by trifluoromethanesulfonic acid-trifluoroacetic acid-dimethyl sulfideJames P. Tam, William F. Heath, and R. B. MerrifieldCite this: J. Am. Chem. Soc. 1986, 108, 17, 5242–5251Publication Date (Print):August 1, 1986Publication History Published online1 May 2002Published inissue 1 August 1986https://doi.org/10.1021/ja00277a031RIGHTS & PERMISSIONSArticle Views4521Altmetric-Citations159LEARN 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 InReddit PDF (1 MB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Lumbar Degenerative Disk Disease (2007)

The sequelae of disk degeneration are among the leading causes of functional incapacity in both sexes and are a common source of chronic disability in the working years. Disk degeneration involves structural disruption and cell-mediated changes in composition. Mechanical, traumatic, nutritional, and genetic factors all may play a role in the cascade of disk degeneration, albeit to variable degree in different individuals. The presence of degenerative change is by no means an indicator of symptoms, and there is a very high prevalence in asymptomatic individuals. The etiology of pain as the symptom of degenerative disease is complex and appears to be a combination of mechanical deformation and the presence of inflammatory mediators. The role of imaging is to provide accurate morphologic information and influence therapeutic decision making. A necessary component, which connects these two purposes, is accurate natural history data. Understanding the relationship of etiologic factors, the morphologic alterations, which can be characterized with imaging, and the mechanisms of pain production and their interactions in the production of symptoms will require more accurate and reproducible stratification of patient cohorts.
Pyrimidinthiones (Part I): Utility of 2-Thioxopyrimidin-6-(1H)ones as Ring Transformer in the Synthesis of Fused Bi- and Tri-Cyclic Heterocyclic Compounds and Their Potential Biological Activities (2008)

The pyrimidinethiones have wide biological and pharmaceutical activities, that have attracted considerable interest in recent years especially as antiviral inhibiting production of hepatitis B virus (HBV), and in vitro insulin-mimetic. Activity of the complexes of pyrimidinone derivatives evaluated from 50% inhibitory concentration promoted us to study the transformation of the 2-thioxopyrimidin-6(1H) ones to fused bi- and tri-cyclic heterocyclic compounds having the pyrimidine moieties and screening their biological activity. The reactivity of 2-mercapto-4-aryl-5-cyanopyrimidin-6(1H)ones (1) towards alkylation by different mono and bifunctional halo-organic compounds has been investigated to give S-monoalkylated products 2, 7 and 9; S- and N-dialkylated products 3, 13 and 14. Treatment of 1 and/or 2 with hydrazine hydrate as a nitrogen nucleophile have been investigated to give 4, treatment of 4 with CS2 and sodium nitrite in the presence of acetic acid (0°C) produced 1,2,4-triazolopyrimidin-5(1H)one derivatives (5)and tetrazolo[1,5-a]pyrimidin-5(1H)ones (6), respectively. Also cyclization of 7 and 9 gave [1,3]thiazolo[3,2-a]pyrimidin-5(1H)one and [1,3]thiazolo[3,2-a]pyrimidin-3,5-dione derivatives 8 and 10 respectively, treatment of 10 with aromatic aldehyde produces 11 which reacted with guanidine HCl to give pyrimido[4,5-d]thiazolo[3,2-a]pyrimidin-6(1H)one derivative 12. Reaction of 14 with o-phenylenediamine was investigated and gave [1,4]quinoxalino[2,3-b][1,3]thiazolo[3,2-a]pyrimidin-9(1H)one derivative 15.
Measuring the Accuracy of Diagnostic Systems (1988)

Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.
A Lightweight Mechanism to Secure OLSR. (2006)

Routing protocols in ad hoc networks are vulnerable to various attacks. Many solutions have been proposed to secure ad hoc routing protocols in recent research but at the price of significant traffic and processing overhead, which may be undesirable for the ad hoc networks with limited bandwidth and processing power. In this paper, we present and evaluate a lightweight mechanism to secure OLSR (Optimized Link State Routing [1]). In our approach, the mechanism of coherence check is applied to secure the link state update. To secure the neighbor establishment, we adopt the idea based on proof introduced in ADVSIG [2]. We identify a security flaw in ADVSIG and then propose a solution to counter it. Besides, we use the hash chain technique to reduce the processing overhead of HELLO messages in the neighbor establishment. Simulation results show that our approach is both lightweight and robust without degrading significantly the performance of OLSR.
Polydopamine Hollow Nanoparticle Functionalized with N‐diazeniumdiolates as a Nitric Oxide Delivery Carrier for Antibacterial Therapy (2016)

A biocompatible nitric oxide (NO) delivery nanoplatform, whose structure is a hollow nanoparticle composed of polydopamine backbone and diazeniumdiolates functional groups, is developed for antibacterial therapy. This platform liberates high NO quantitis and exerts the antibacterial activity with excellent biocompatibility thus being promising for treating bacterial infections.
Atomic Layer Deposition of Lithium Tantalate Solid-State Electrolytes (2013)

3D all-solid-state microbatteries are promising onboard power systems for autonomous devices. The fabrication of 3D microbatteries needs deposition of active materials, especially solid-state electrolytes, as conformal and pinhole free thin films in 3D architectures, which has proven very difficult for conventional deposition techniques, such as chemical vapor deposition and physical vapor deposition. Herein, we report an alternative technique, atomic layer deposition (ALD), for achieving ideal solid-state electrolyte thin films for 3D microbatteries. Lithium tantalate solid-state electrolytes, with well-controlled film composition and film thickness, were grown by ALD at 225 °C using subcycle combination of 1 × Li2O + n × Ta2O5 (1 ≤ n ≤ 10). The film composition was tunable by varying Ta2O5 subcycles (n), whereas the film thickness displayed a linear relationship with ALD cycle number, due to the self-limiting nature of the ALD process. Furthermore, the lithium tantalate thin films showed excellent uniformity and conformity in 3D anodic aluminum oxide template. Moreover, impedance testing showed that the lithium tantalate thin film exhibited a lithium ion conductivity of 2 × 10–8 S/cm at 299 K. The lithium tantalate thin films by ALD, featured with well-controlled film thickness and composition, excellent step coverage, and moderate ionic conductivity at room temperature, would be promising solid-state electrolytes for 3D microbatteries.
Studies on the Metabolism of Retinol and Retinol-binding Protein in Transthyretin-deficient Mice Produced by Homologous Recombination (1995)

Tissue needs for retinoids are believed to be satisfied through the delivery in the circulation of retinol by its specific plasma transport protein, retinol-binding protein (RBP), which circulates as a 1-to-1 protein complex with transthyretin (TTR). The binding of RBP to TTR is thought to prevent filtration of retinol-RBP in the kidney and to play a role in secretion of RBP from hepatocytes. Recently a strain of mice (TTR-) that totally lacks immunoreactive TTR was produced by targeted mutagenesis. We have explored the effects of TTR deficiency on retinol and RBP metabolism in this mutant strain. In pooled plasma from the TTR- mice retinol levels averaged 6% of those of wild type animals. Similarly, plasma RBP in the TTR- mice was found to be 5% of wild type levels. Hepatic retinol and retinyl ester levels were similar for mutant and wild type mice, suggesting that the mutation affects neither the uptake nor storage of dietary retinol. Levels of retinol and retinyl esters in testis, kidney, spleen, and eye cups from TTR- mice were normal. Plasma all-trans-retinoic acid levels for the TTR- mice were 2.3-fold higher than those of wild type (425 versus 190 ng/dl). Kidney RBP levels were similar for the mutant and wild type mice and we were unable to detect intact RBP in urine from TTR- mice. Hepatic RBP levels in the TTR- mice were 60% higher than those of wild type mice (39.8 versus 25.0 micrograms of RBP/g of tissue). These data may suggest that there is a partial blockage in RBP secretion from TTR- hepatocytes that leads to lessened plasma levels of retinol-RBP.
Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA (2012)

The modified base 5-methylcytosine (m(5)C) is well studied in DNA, but investigations of its prevalence in cellular RNA have been largely confined to tRNA and rRNA. In animals, the two m(5)C methyltransferases NSUN2 and TRDMT1 are known to modify specific tRNAs and have roles in the control of cell growth and differentiation. To map modified cytosine sites across a human transcriptome, we coupled bisulfite conversion of cellular RNA with next-generation sequencing. We confirmed 21 of the 28 previously known m(5)C sites in human tRNAs and identified 234 novel tRNA candidate sites, mostly in anticipated structural positions. Surprisingly, we discovered 10,275 sites in mRNAs and other non-coding RNAs. We observed that distribution of modified cytosines between RNA types was not random; within mRNAs they were enriched in the untranslated regions and near Argonaute binding regions. We also identified five new sites modified by NSUN2, broadening its known substrate range to another tRNA, the RPPH1 subunit of RNase P and two mRNAs. Our data demonstrates the widespread presence of modified cytosines throughout coding and non-coding sequences in a transcriptome, suggesting a broader role of this modification in the post-transcriptional control of cellular RNA function.
Chitin particle-induced cell-mediated immunity is inhibited by soluble mannan: mannose receptor-mediated phagocytosis initiates IL-12 production (1997)

Previous studies showed that mouse spleen cells produced IL-12, TNF-alpha, and IFN-gamma when stimulated with phagocytosable-size chitin particles (N-acetyl-D-glucosamine polymers). To dissect the mechanisms of the cytokine production in this study, spleen cells from BALB/c mice were cultured with 1 to 10 microm chitin particles, heat-killed Corynebacterium parvum vaccine, zymosan, and mannan (a mannose polymer)-coated latex beads (1 microm) at 1, 10, or 100 microg/ml. We found that these particles induced IL-12, TNF-alpha, and IFN-gamma. However, these cytokines were not produced when spleen cells were cultured with soluble chitin, mannan, or laminarin (a polymer of beta-glucan), 1 to 10 microm beta-glucan particles, laminarin-coated latex beads, 1 microm latex beads, 50 to 100 microm chitin particles, or 50 to 100 microm mannan-coated beads. Soluble mannan, but not soluble laminarin, inhibited cytokine production following stimulation with 1 to 10 microm chitin particles, zymosan, or heat-killed C. parvum. In addition, cytochalasin D also inhibited cytokine production. The treatments with soluble mannan or with cytochalasin D, in sharp contrast, did not inhibit LPS-induced IL-12/IFN-gamma production or exogenous IL-12-induced IFN-gamma production. Finally, spleen cells from C3H/HeJ mice also showed comparable levels of IL-12/TNF-alpha/IFN-gamma production when induced by 1 to 10 microm chitin particles. Taken together, our results indicate that mannose receptor-mediated phagocytosis, but not the receptor-mediated pinocytosis, is highly associated with the production of IFN-gamma-inducing extracellular signaling factors such as IL-12 and TNF-alpha. The novel mechanism of phagocytosis-dependent IL-12 production appears to be distinct from that of LPS-induced cytokine production.