gebhart/patrepeval huggingface dataset:
Receptors : model systems and specific receptors (1993)

Steroid receptors in the central nervous system, L.M. Freeman and S.M. Breedlove membrane receptor for glucocorticoids in mammalian neurons, Y. Cehn, et al interleukin-1 receptors in the brain-endocrine-immune axis, T. Takao and E.B. De Souza vasoactive peptides and their receptors, D. Regoli, et al melanotropin receptors of the brain, J.B. Tatro melatonin binding sites, E.L. Bittman transferrin receptors in the central nervous system, B. Giometto, et al binding sites of pituitary adenylate cyclase activating polypeptide (PACAP) in human brain, D.M. Smith and S.R. Bloom role of cholecystokinin type B receptor in nociception studied with peptide agonists and antagonists, Z. Wiesenfeld Hallin and X.-J. Xu cholecystokinin receptors - radioligand binding and affinity labeling, M.P. Lutz and L.J. Miller endothelin receptors in neural systems, P.G. Lysko and P. Nambi natriuretic peptide receptors, V.T.F. Yeung, et al structural and functional identification of insulinlike growth factor receptors, S. Gammeltoft methods for studying central serotonergic receptors, P.M. Whitaker-Azmitia analysis of serotonin 5-HT1A receptors in primary neuronal culture, B.C. Swarzenski, et al characterization of the bombesin/GRP receptor in Swiss 3T3 fibroblasts, I. Zachary, et al receptors for bombesin-like peptides in the rat central nervous system, E.E. Ladenheim, et al retinal insulin receptors, S.A. Rosenzweig pancreatic polypeptide receptors in rat brain, D.C. Whitcomb neurotensin receptors in primary culture of neurons, J. Mazella, et al analysis of the structure and function of the fast nerve growth factor receptor, A.A. Welcher solubilization and physicochemical characterization of 5-HT3 receptor binding sites, M.C. Miquel, et al solubilization and characterization of the receptor for gastrin-releasing peptide, R. Kris, et al assays for pituitary adenylate cyclase activatin peptide (PACAP) receptors coupled to adenylate cyclase - comparison between rat brain and human neuroblastoma cells, J. Christophe, et al.
Improvement of the quality factor of RF integrated inductors by layout optimization (2000)

A systematic method to improve the quality (Q) factor of RF integrated inductors is presented in this paper. The proposed method is based on the layout optimization to minimize the series resistance of the inductor coil, taking into account both ohmic losses, due to conduction currents, and magnetically induced losses, due to eddy currents. The technique is particularly useful when applied to inductors in which the fabrication process includes integration substrate removal. However, it is also applicable to inductors on low-loss substrates. The method optimizes the width of the metal strip for each turn of the inductor coil, leading to a variable strip-width layout. The optimization procedure has been successfully applied to the design of square spiral inductors in a silicon-based multichip-module technology, complemented with silicon micromachining postprocessing. The obtained experimental results corroborate the validity of the proposed method. A Q factor of about 17 have been obtained for a 35-nH inductor at 1.5 GHz, with Q values higher than 40 predicted for a 20-nH inductor working at 3.5 GHz. The latter is up to a 60% better than the best results for a single strip-width inductor working at the same frequency.
Site-Specific, Covalent Attachment of Proteins to a Solid Surface (2006)

Immobilized and site-specifically labeled proteins are becoming invaluable tools in proteomics. Here, we describe a strategy to attach a desired protein to a solid surface in a covalent, site-specific manner. This approach employs an enzymatic posttranslational modification method to site-specifically label a target protein with an azide; an alternative substrate for protein farnesyl transferase containing an azide group was developed for this purpose. A bio-orthogonal Cu(I)-catalyzed cycloaddition reaction is then used to covalently attach the protein to agarose beads bearing an alkyne functional group. We demonstrate that both the azide incorporation and the capture steps can be performed on either a purified protein target or on a protein present within a complex mixture. This approach involves the use of a four-residue tag which is significantly smaller than most other tags reported to date and results in covalent immobilization of the target protein. Hence it should have significant applicability in protein science.
Abl Tyrosine Kinase Phosphorylates Nonmuscle Myosin Light Chain Kinase to Regulate Endothelial Barrier Function (2010)

Nonmuscle myosin light chain kinase (nmMLCK), a multi-functional cytoskeletal protein critical to vascular homeostasis, is highly regulated by tyrosine phosphorylation. We identified multiple novel c-Abl-mediated nmMLCK phosphorylation sites by mass spectroscopy analysis (including Y231, Y464, Y556, Y846) and examined their influence on nmMLCK function and human lung endothelial cell (EC) barrier regulation. Tyrosine phosphorylation of nmMLCK increased kinase activity, reversed nmMLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhanced binding to the critical actin-binding phosphotyrosine protein, cortactin. EC challenge with sphingosine 1-phosphate (S1P), a potent barrier-enhancing agonist, resulted in c-Abl and phosphorylated nmMLCK recruitment into caveolin-enriched microdomains, rapid increases in Abl kinase activity, and spatial targeting of c-Abl to barrier-promoting cortical actin structures. Conversely, reduced c-Abl expression in EC (siRNA) markedly attenuated S1P-mediated cortical actin formation, reduced the EC modulus of elasticity (assessed by atomic force microscopy), reduced nmMLCK and cortactin tyrosine phosphorylation, and attenuated S1P-mediated barrier enhancement. These studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK and strongly support c-Abl-cortactin-nmMLCK interaction as a novel determinant of cortical actin-based cytoskeletal rearrangement critical to S1P-mediated EC barrier enhancement.
Effect of a calcium-enriched diet on the colonic epithelial hyperproliferation induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats on a low calcium and fat diet. (1990)

We examined whether hyperproliferation of colonic crypt epithelium during cancer induction by N-methyl-N-nitro-N-nitrosoguanidine (MNNG), in rats on a low fat and calcium diet could be reduced by added calcium p.o. From the age of 4 weeks, 104 male Sprague-Dawley rats received a low fat (3.5%), low calcium (0.05% calcium ion), and low vitamin D (0.4 IU/g) diet. Sixty-four also had calcium salts, derived from either calcium lactate or solubilized calcium carbonate, added to their drinking water; therefore their total calcium intake was about 1% of daily diet. At age 12 weeks the rats were divided into 4 treatment groups: 8 rats, not receiving added calcium, had rectal saline instillations weekly (saline control group) and were sacrificed after a further 28 weeks; 3 groups of 32 rats each received intrarectal MNNG (1.5 mg) weekly. One group, not receiving added calcium, was the MNNG control group; while the second group also received added calcium lactate, and the third group received calcium carbonate. Groups of 24 were sacrificed periodically until 28 weeks of treatment. Rats were sacrificed and epithelial proliferation was estimated, 1 week after the last intrarectal instillation, by in vivo labeling with tritiated thymidine and measuring the ratio of labeled to total colonic crypt epithelial cells. The mean labeling index of the MNNG treated and added calcium groups were significantly higher (8.7-9.5%) than that of the saline controls (2.8%) only at week 28; however, it was then still significantly less than that of the MNNG controls not having added calcium (17.9%). Hyperproliferation, during induction of colonic cancer by MNNG in rats on a low calcium diet, can be reduced by a calcium enriched diet even in the presence of a low fat intake.
Pyrimidines. XIII. 2‐ and 6‐substituted 4‐pyrimidinecarboxylic acids (1964)

Abstract The “abnormal” behavior of 4,6‐dimethyl‐2‐pyrimidinol towards nitrous acid has been clarified. The reaction between 4‐methyl‐2‐pyrimidinol and nitrous acid has been utilized as a new synthetic procedure for the preparation of several 2‐substituted 4‐pyrimidinecarboxylic acids. 2‐Hydroxy‐4‐pyrimidinecarboxylic acid has also been prepared from 4‐chloro‐2‐methylthiopyrimidine via the trimethylammonium intermediate. 6‐Amino‐ and 6‐thio‐4‐pyrimidinecarboxylic acids have been readily prepared from the previously reported 6‐hydroxy‐4‐pyrimidinecarboxylic acid.
User-friendly access control for public network ports (1999)

We are facing a growing user demand for ubiquitous Internet access. As result, network ports and wireless LANs are becoming common in public spaces inside buildings such as lounges, conference rooms and lecture halls. This introduces the problem of protecting networks accessible through these public ports from unauthorized use. In this paper, we study the problem of access control through public network ports. We view this problem as a special case of the more general problem of access control for a service on a network. We present an access control model on which we base our solution. This model has three components: authentication, authorization, and access verification. We describe the design and implementation of a system that allows secure network access through public network ports and wireless LANs. The design requires no special hardware or custom client software, resulting in minimal deployment cost and maintenance overhead. The system has a user-friendly, Web-based interface, offers good security, and scales to a campus-sized community.
Spectroscopic spectral-domain optical coherence microscopy (2006)

The spectroscopic content within optical coherence tomography (OCT) data can provide a wealth of information. Spectroscopic OCT methods are frequently limited by time-frequency trade-offs that limit high spectral and spatial resolution simultaneously. We present spectroscopic spectral-domain optical coherence microscopy performed with a multimodality microscope. Restricting the spatial extent of the signal by using high-numerical-aperture optics makes high-resolution spectroscopic information accessible, facilitated with spectral-domain detection. Simultaneous acquisition of multiphoton microscopy images is used to validate tissue structure and localization of nuclei within individual cells.
The Therapeutic Potential of the Wnt Signaling Pathway in Bone Disorders (2011)

The Wnt pathway plays a critical role in development and differentiation of many tissues, such as the gut, hair follicles, and bone. Increasing evidence indicates that Wnts may function as key regulators in osteogenic differentiation of mesenchymal stem cells and bone formation. Conversely, aberrant Wnt signaling is associated with many osteogenic pathologies. For example, genetic alterations in the Wnt signaling pathway lead to osteoporosis and osteopenia, while inactivating mutations of Wnt inhibitors result in a hyperostotic skeleton with increased bone mineral density. Hyperparathyroidism causes osteopenia via induction of the Wnt signaling pathway. Lithium, often used to treat bipolar disorder, blocks a Wnt antagonist, decreasing the patient's risk of fractures. Thus, manipulating the Wnt pathway may offer plenty therapeutic opportunities in treating bone disorders. In fact, induction of the Wnt signaling pathway or inhibition of Wnt antagonists has shown promise in treating bone metabolic disorders, including osteoporosis. For example, antibodies targeting the Wnt inhibitor Sclerostin lead to increased bone mineral density in post-menopausal women. However, such therapies targeting the Wnt pathway are not without risk, as genetic alternations may lead to over-activation of Wnt/β-catenin and its association with many tumors. It is conceivable that targeting Wnt inhibitors may predispose the individuals to tumorigenic phenotypes, at least in bone. Here, we review the roles of Wnt signaling in bone metabolic and pathologic processes, as well as the therapeutic potential for targeting Wnt pathway and its associated risks in bone diseases.
Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal cells by microsatellite analysis. (2001)

Prompt detection of head and neck squamous cell carcinoma (HNSCC) is vital to successful patient management. In this feasibility study, we used microsatellite analysis to detect tumor-specific genetic alterations in exfoliated oral mucosal cell samples from patients with known cancer. Exfoliated mucosal cells in pretreatment oral rinse and swab samples were collected from 44 HNSCC patients and from 43 healthy control subjects (20 nonsmokers and 23 smokers). We tested a panel of 23 informative microsatellite markers to assay DNA from the matched lymphocyte, tumor (from cancer cases), and oral test samples. Loss of heterozygosity or microsatellite instability of at least one marker was detected in 38 (86%) of 44 primary tumors. Identical alterations were found in the saliva samples in 35 of these 38 cases (92% of those with markers; 79% overall) including 12 of 13 cases with small primaries [stage Tt or Tx (occult primary)] and 4 of 4 cases of patients that had undergone prior radiation. Microsatellite instability was detectable in the saliva in 24 (96%) of 25 cases in which it was present in the tumor, and loss of heterozygosity was identified in the test sample in 19 (61%) of 31 cases. No microsatellite alterations were detected in any of the samples from the healthy control subjects. This approach must now be refined and validated for the detection of clinically occult disease. Microsatellite analysis of oral samples may then become a valuable method for detecting and monitoring HNSCC.
Increased serum concentrations of secretory leukoprotease inhibitor in patients with primary Sjögren's syndrome. (1999)

Determination of serum SLPI may provide a new simple noninvasive technique for evaluation of primary SS.
An articulated neurosurgical navigation system using MRI and CT images (1988)

Neurosurgical operations sometimes involve difficulties in finding out the real positions of small-size neoplasms shown on tomographical images. The articulated navigation system, with the aid of a computer, gives ongoing positional correspondence between the position in the patient's brain and the one in the tomographic images to assist neurosurgery.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Equilibration and temperature distribution in a driven ion chain (2011)

We study thermalization and non-equilibrium dynamics in a dissipative quantum many-body system -- a chain of ions with two points of the chain driven by thermal bath under different temperature. Instead of a simple linear temperature gradient as one expects from the classical heat diffusion process, the temperature distribution in the ion chain shows surprisingly rich patterns, which depend on the ion coupling rate to the bath, the location of the driven ions, and the dissipation rates of the other ions in the chain. Through simulation of the temperature evolution, we show that these unusual temperature distribution patterns in the ion chain can be quantitatively tested in experiments within a realistic time scale.
The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition (1994)

The relationship between four pharmacologically distinct NMDA receptor subtypes, identified in radioligand binding studies, and the recently identified NMDA receptor subunits (NR1a-g, NR2A-D) has not been determined. In this report, we demonstrate that the anatomical distribution of the four NMDA receptor subtypes strikingly parallels the distribution of mRNA encoding NR2A-D subunits. The distribution of NR2A mRNA was very similar to that of "antagonist-preferring" NMDA receptors [defined by high-affinity 3H-2-carboxypiperazine-4-yl-propyl-1-phosphonic (3H-CPP) binding sites; correlation coefficient = 0.88]. Agonist-preferring NMDA receptors localized to brain regions expressing both NR2B mRNA and NR1- mRNA (NR1 splice variant lacking insert 1). NR2C mRNA was largely restricted to the cerebellar granule cell layer, a region that displays a unique pharmacological profile. NR2D mRNA localized exclusively to those diencephalic nuclei that have a fourth, distinct pharmacological profile (typified by the midline thalamic nuclei). The pharmacology of native NMDA receptors was compared to that of heteromeric NMDA receptors expressed in Xenopus oocytes (NR1/NR2A, NR1/NR2B, NR1/NR2C). The oocyte-expressed NR1/NR2A receptor displayed a higher affinity for antagonists and a slightly lower affinity for agonists than the NR1/NR2B receptor. These patterns are analogous to those found for radioligand binding to native receptors in the lateral thalamus and medial striatum, respectively. NMDA receptors in the lateral thalamus (with a high density of NR2A subunit mRNA) displayed higher affinity for antagonists and a lower affinity for agonists than did NMDA receptors of the medial striatum (a region rich in NR2B mRNA). Relative to the NR1/NR2A and NR1/NR2B receptors, oocyte-expressed NR1/NR2C receptors had a lower affinity specifically for both D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (D-CPPene) and homoquinolinate (HQ). This pattern was identical to that observed for cerebellar (NR2C-containing) versus forebrain (NR2A- and NR2B-containing) NMDA receptors. Taken together, the data in this report suggest that the four previously identified native NMDA receptor subtypes differ in their NR2 composition. Furthermore, the NR2 subunits significantly contribute to the anatomical and pharmacological diversity of NMDA receptor subtypes.
39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. (1991)

A 39-kDa protein of unknown function has previously been reported to copurify with the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor. In this study we demonstrate that a recombinant 39-kDa fusion protein can reversibly bind to the 515-kDa subunit of the LRP/alpha 2-macroglobulin receptor. This interaction inhibits the binding and uptake of the receptor's two known ligands: 1) beta-migrating very low density lipoproteins activated by enrichment with apoprotein E and 2) alpha 2-macroglobulin activated by incubation with plasma proteases or methylamine. A potential in vivo role of the 39-kDa protein is to modulate the uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in hepatic and extrahepatic tissues.
Experimental Treatments for Neovascular Age-Related Macular Degeneration (2012)

C. V. Regatieri1,3, J. L. Dreyfuss2,4 and H. B. Nader2 1Departmento de Oftalmologia, 2Departmento de Bioquimica, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, 3Schepens Eye Research Institute, Harvard Medical School, Department of Ophthalmology, Boston, 4Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, 1,2Brazil 3,4USA
The frequency of previously undetectable deletions involving 3′ Exons of the PMS2 gene (2012)

Lynch syndrome is characterized by mutations in one of four mismatch repair genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in PMS2 has previously been confined to Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method that permits detection of deletions of PMS2 Exons 12-15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3' deletions in 58 samples that were reported to be negative for PMS2 mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3' region of PMS2, including three previously reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15. Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through Alu-mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a PMS2 mutation based on immunohistochemical staining, for which mutations have not yet been identified, would benefit from testing using the new methodology.
Clinical Uses of Tumor Markers: A Critical Review (2001)

Tumor markers are molecules that indicate the presence of malignancy. They are potentially useful in cancer screening, aiding diagnosis, assessing prognosis, predicting in advance a likely response to therapy, and monitoring patients with diagnosed disease. Because of the low prevalence of most cancers in the general population and the limited sensitivity and specificity of available markers, these tests alone are generally of little value in screening for cancer in healthy subjects. Currently, however, PSA in combination with digital rectal examination and CA 125 together with ultrasound are undergoing evaluation as screening modalities for prostate and ovarian cancer, respectively. Again, because of a lack of sensitivity and specificity, markers are rarely of use in the early diagnosis of cancer. As prognostic indicators, markers may provide information that is independent of traditionally used factors or within subgroups defined by traditional criteria, for example, urokinase plasminogen activator in node-negative breast cancer. At present, the best available marker for predicting response to therapy is the estrogen receptor for selecting hormone-sensitive breast cancers. Many different markers can be used in the surveillance of patients with diagnosed malignancies, the most useful of these being HCG in trophoblastic disease and both AFP and HCG for nonseminomatous testicular germ cell tumors. In general, the currently available tumor markers lack sensitivity for early cancer and specificity for malignancy. The goal of future research should be to develop more sensitive and specific markers, especially for the common cancers.
Dissociating Quaternary Structure Regulates Cell-signaling Functions of a Secreted Human tRNA Synthetase (2011)

Many tRNA synthetases are homodimers that are catalytically inactive as monomers. An example is the 528-amino acid human tyrosyl-tRNA synthetase, which is made up of an N-terminal catalytic unit (TyrRS(Mini)) and a 164-amino acid C-domain. Although native TyrRS has no known cytokine functions, natural proteolysis of secreted TyrRS releases TyrRS(Mini), which not only has the same aminoacylation activity as native TyrRS but also has strong activity for stimulating migration of polymorphonuclear leukocytes. The migration-stimulating activity is dependent on an ELR tripeptide motif, similar to that in CXC cytokines like IL-8, and also has the familiar bell-shaped concentration dependence seen for CXC cytokines. Here we show that in contrast to IL-8, where the bell-shaped dependence arises from the effects of CXCR1/2 receptor internalization, TyrRS(Mini) does not induce internalization of CXCR1/2. A rationally designed non-associating monomer and a non-dissociating dimer were constructed. With these constructs, the bell-shaped concentration dependence of leukocyte migration was shown to arise from the agonist (for migration) activity of the catalytically inactive monomer and the antagonist activity of the catalytically active dimer. Thus, the dissociating quaternary structure of TyrRS(Mini) regulates two opposing cytokine activities and suggests the possibility of dissociating quaternary structures regulating novel functions of other tRNA synthetases.