gebhart/patrepeval huggingface dataset:
Disease-causing mutations in the CLRN1 gene alter normal CLRN1 protein trafficking to the plasma membrane. (2009)

WT CLRN1 is a glycoprotein localized to the plasma membrane in transfected BHK-21 cells. Mutant CLRN1 proteins are mislocalized. We suggest that part of the pathogenesis of USH3 may be associated with defective intracellular trafficking as well as decreased stability of mutant CLRN1 proteins.
From cells to signaling cascades: manipulation of innate immunity byToxoplasma gondii (2003)

The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus for cell-mediated immunity, and IL-12-dependent IFN-gamma induction is vital in resistance to the parasite. Dendritic cells, neutrophils and macrophages are important sources of IL-12 during infection. T. gondii possesses two mechanisms for triggering IL-12. One is dependent upon the common adaptor protein MyD88, and is likely to involve Toll-like receptors. The other is a more unusual pathway that involves triggering through CCR5 by a parasite cyclophilin molecule. Countering these potent pro-inflammatory activities, T. gondii has several mechanisms to down-regulate immunity. Intracellular infection causes a blockade in the NFkappaB macrophage signaling pathway, correlating with reduced capacity for IL-12 and TNF-alpha production. The parasite also prevents STAT1 activity, resulting in decreased levels of IFN-gamma-stimulated MHC surface antigen expression. Furthermore, infection also induces resistance to apoptosis through inhibition of caspase activity. Extracellular pathways of suppression involve soluble mediators such as IL-10 and lipoxins that have potent IL-12 down-regulatory effects. The balance of pro-inflammatory and anti-inflammatory signaling which T. gondii engages is likely dictated by requirements for a stable host-parasite interaction. First, there is a need for Toxoplasma to induce an immune response robust enough to allow host survival and establish long-term chronic infection. Second, the parasite must avoid immune-elimination and induction of pro-inflammatory pathology that can cause lethality if unchecked. The widespread distribution of T. gondii and the normally innocuous nature of infection indicate the skill with which the parasite achieves the two seemingly contrary goals.
Identification of Residues Responsible for Ligand Recognition and Regioisomeric Selectivity of Lysophosphatidic Acid Receptors Expressed in Mammalian Cells (2005)

The endothelial differentiation gene family encodes three highly homologous G protein-coupled receptors for lysophosphatidic acid (LPA). Based on baculoviral overexpression studies, differences have been proposed in the structure-activity relationship (SAR) of these receptors. We have compared the SAR of the individual receptors either overexpressed transiently at high or at lower levels following stable transfection in LPA-nonresponsive RH7777 cells. The SAR in transfected RH7777 cells was markedly different from that described in insect cells. The LPA(3) receptor has been proposed to be selectively activated by unsaturated LPA species and shows a strong preference for sn-2 versus the sn-1 acyl-LPA regioisomer. Because of the short half-life of sn-2 LPA due to acyl migration under some conditions, we have synthesized acyl migration-resistant analogs using an acetyl group in place of the free hydroxyl group in order to evaluate LPA receptor SAR. Only LPA(1) and LPA(2) showed regioisomeric preference and only for the 18:2 fatty acyl-stabilized LPA sn-1 regioisomer. To identify residues involved in ligand recognition of LPA(3), we developed and validated computational models of LPA(3) complexes with the analogs studied. The models revealed that Arg-3.28 and Gln-3.29 conserved within the LPA-selective endothelial differentiation gene receptors and the more variable Lys-7.35 and Arg-5.38 of LPA(3) form critical interactions with the polar headgroup of LPA. The models identified Leu-2.60 and Val-7.39 of LPA(3) underlying the regioisomer-selective interaction with the acetyl group of the stabilized regioisomers. Mutation of Leu-2.60 to alanine selectively increased the EC(50) of the sn-2 acetyl-LPA regioisomers, whereas alanine replacement of Val-7.39 profoundly affected both regioisomers.
Electro-optical and nonlinear optical properties of semiconductor nanorod doped liquid crystals (2005)

We studied the electro-optical property and photorefractive effects in a semiconductor CdSe nanorod doped neamtic liquid crystal [NLC] system. The nonlinear index coefficient is measured to be <i>n</i><sub>2</sub>=2.05×10<sup>&minus;2</sup><i>cm</i><sup>2</sup>/<i>W</i>, which is 10 times larger than that of an equivalent pure liquid crystal system. Electro-optical switching investigation shows that the Freedericksz transition voltage of this system is also noticeably lower than that of un-doped NLC. These enhanced electro- and nonlinear optical properties are attributed to the photoconductivity of CdSe nanorods and the enlarged electric conductivity and dielectric anisotropies of the doped system. An AC field assisted photorefractive effect in CdSe nanorod doped liquid crystal system has also been studied.
Evidence for a structurally-driven insulator-to-metal transition inVO2: A view from the ultrafast timescale (2004)

We apply ultrafast spectroscopy to establish a time-domain hierarchy between structural and electronic effects in a strongly correlated electron system. We discuss the case of the model system ${\mathrm{VO}}_{2}$, a prototypical nonmagnetic compound that exhibits cell doubling, charge localization, and a metal-insulator transition below 340 K. We initiate the formation of the metallic phase by prompt hole photo-doping into the valence band of the low-$T$ insulator. The insulator-to-metal transition is, however, delayed with respect to hole injection, exhibiting a bottleneck time scale, associated with the phonon connecting the two crystallographic phases. This structural bottleneck is observed despite faster depletion of the $d$ bands and is indicative of important bandlike character for this controversial insulator.
Histamine: Biology and Medical Aspects (2004)

Preface: Histamine, the Oldest Biogenic Amine, Revisited in the New Millennium: Watanabe, T. Introduction: Falus, A. 1. Histamine Biology Histamine: Fundamentals of Biological Chemistry: Noszal, B. Kraszni, M. Racz, A. 2. Enzymes in Histamine Metabolism Histidine Decarboxylase (HDC) Enzyme and Gene: Darvas, Z. Falus, A. Diamine Oxidase (DAD) Enzyme and Gene: Schwelberger, H.G. Histamine N-Methyltransferase (HNMT) Enzyme and Gene: Schwelberger, H.G. 3. Histamine Receptors Histamine Receptors: H1, H2, H3, H4, and the Putative 'Hic' (Intracellular) Receptor. Coding Genes and Gene Products, 'in silico' and Experimental Data: Igaz, P. Hargita, H. Histamine Agonists, Antagonists, and Inverse Agonists: Tomoskozi, Z. Signal-Transduction Pathways of Histamine Receptors: Lazar-Molnar, E. 4. Histamine in the Immune System Characterization of Histamine Release by Mast Cells, Basophils, and Monocytes: Watt, A.P. Ennis, M. Cytokines, Chemokines, and Histamine: Igaz, P. Falus, A. Complement Activation and Histamine Release: Erdei, A. Andrasfaivy, M. The Role of Histamine in the Hepatic Acute Phase Reaction and Systemic Inflammation: Fillop, A.K. Histamine and Sepsis: Matauds, N. Hattorl, Y. Gando, S. Histamine in Allergy: Herjavecz, I. Hirschberg, A. 5. Histamine in the Gastrointestinal System Histamine and Gastric Ulcer. Secretory and Inflamatory Histamine in the Stomach: Hunyady, B. Histamine in Food: Sarkadi, L. Histamine Neurons Activated by Mastication Satiate Appetite and Upregulate Their Energy Expenditure: Sakata, T. 6. Histamine in Cell Proliferation and Differentiation Histamine and Cell Proliferation: Pos, Z. Hegyesi, H. Rivera, E.S. Histamine and Polyamines: Laszio, V. Histamine and Hematopoiesis: Schneider, E. Dy, M. Histamine in Embryonic Development: Karlstedt, K. Panula, P. 7. Histamine in the Nervous System Histamine as a Neurotransmitter in the Central Nervous System: Yanal, K. Watanabe, T. Histamine and the Blood-Brain Barrier: Deli, M.A. Abraham, C.S. Histamine in CNR-Resident Non-Neural Cells: Huszti, Z. Histamine in Neuroendocrine Regulation: Kovacs, K.J. The Influence of Histamine on Memory: Passani, M.B. Cangioli, I. Blandina, P. 8. Other Medical Aspects of Histamine Histamine and the Cardiovascular System: Jochem, J. Zwirska-Korczals, K.W. Connection between Histamine and the Sexual Steroids: Pap, E. Histamine and Surgery: Celik, I. Lorenz, W. 9. Conclusion Lessons from the HDC-KO Mice Newly Recognized Aspects of Histamine Biology: Watanabe, T. Falus, A. Subject Index
Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib (2015)

In chronic lymphocytic leukemia (CLL), patients with unmutated immunoglobulin heavy chain variable region gene (UM-CLL) have worse outcomes than mutated CLL (M-CLL) following chemotherapy or chemoimmunotherapy. However, in the era of BCR-targeted therapies, the adverse prognostic impact of unmutated IGHV seems to be diminishing, and there are clinical datasets showing unexpected improved responses in UM-CLL. We investigated the biological differences of BTK activity between these subgroups and further compared the impact of ibrutinib on molecular and cellular behaviors. Immunoblotting analysis revealed that phosphorylated active BTK is significantly higher in UM-CLL. Moreover, UM-CLL, compared to M-CLL, displayed a much higher proliferative capacity that was correlated with higher phospho-BTK and greater sensitivity to ibrutinib. In addition, BTK depletion with siRNA led to a more prominent reduction in the proliferation of UM-CLL, suggesting that elevated BTK activity is responsible for increased cell proliferation. Further, cell signaling activity by multiple measurements was consistently higher in UM-CLL accompanied by a higher sensitivity to ibrutinib. These studies link UM-CLL to elevated BCR signaling, heightened BTK-dependent cell proliferation and increased sensitivity to ibrutinib. The prognostic significance of IGHV mutation should be reevaluated in the era of new therapies targeting BCR signaling.
If architecture is a system of enclosures and networks, now, with the information networks, buildings acquire a kind of nervous system (2004)

In this interview, William J. Mitchell, a renowned US architect and theoretician, and former Dean of the School of Architecture
and Planning at MIT, explains his theories on the redefinition of space determined by the changes brought on
by IT in society and culture, the relation between networks and architecture, the merging of both virtual and physical
spaces, the effects of mobile technologies on the perception of distance and space, the economy of presence in
terms of the changes produced by IT, and the re-evaluation of place.
Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog (2007)

We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MVo(2)) and oxygen delivery during pregnancy. Awake dogs were studied using echocardiography before and at 40 days, 50 days, and 60 days (60D) of pregnancy and at approximately 14 days postpartum. Left ventricular eNOS, phosphorylated eNOS, and copper, zinc-superoxide dismutase (CuZnSOD or SOD-1) were determined by immunoblotting. MVO(2) of left ventricular tissue samples was measured in vitro in response to increasing doses of bradykinin, enalapril maleate, and amlodipine. We examined the changes in passive diameter and flow-dependant arteriolar dilation of coronary arterioles. Echocardiography indicated increases in cardiac output ( approximately 60%) during pregnancy. Myocardial eNOS (21 +/- 4%), phosphorylated eNOS (19 +/- 3%), and SOD-1 (61 +/- 2.7%) protein levels were significantly increased at 60D. Bradykinin, enalapril maleate, and amlodipine (10(-4) mol/l) decreased MVO(2) in a nitric oxide-dependant manner (by 24 +/- 1.3% in controls and 34 +/- 2.2% at 60D; by 21 +/- 1.1% in controls and 29 +/- 1.1 at 60D; and by 22 +/- 2.5% in controls and 26 +/- 1.0% at 60D, respectively). Arterioles from pregnant dogs showed increased flow-dependant dilation in response to increased shear stress and larger passive diameter. Nitrite production was stimulated by bradykinin and carbachol in microvessels in vitro; pregnancy enhanced nitrite release. Myocardial eNOS, phosphorylated eNOS, and SOD-1 protein expression are increased during pregnancy, and this increase is associated with enhanced nitric oxide-dependant control of MVO(2). Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy.
The murine NPY‐1 receptor gene Structure and delineation of tissue‐specific expression (1992)

The murine gene for the NPY-1 receptor subtype for neuropeptide Y was characterized by DNA sequencing and expression studies. It comprises three exons with a 6,400 bp 5'-untranslated and a 80 bp internal intronic sequence. The 5'-flanking region of this gene lacks TATA or CCAAT consensus sequences in the proximity to the multiple transcription initiation sites. A 1,300 bp genomic fragment of the 5'-flanking region drives the expression of the lacZ reporter gene in NG108-15 cells and primary cultured neurons but not in glial and human embryonic kidney cells. In addition, it contains consensus sequences for various transcription factors including cAMP- and glucocorticoid-responsive elements.
pH-Controlled Selective Protection of Polyaza Macrocycles (1997)

Piperazine (1), tetraazacyclododecane 3 and pentaazacyclopentadecane 4 react with chloroformates in acid solution to give the selectively protected carbamate derivatives 1a, 3a-d, and 4a. The benzyloxycarbonyl derivatives 3d and 4a were alkylated with tert-butyl bromoacetate and removal of the benzyloxycarbonyl protection by catalytic hydrogenation afforded tert-butyl esters 5b and 6b in good yields.
Nucleic acid amplification-based diagnosis of respiratory virus infections (2010)

The appearance of eight new respiratory viruses in the human population in the past 9 years, including two new pandemics (SARS coronavirus in 2003 and swine-origin influenza A/H1N1 in 2009), has tested the ability of virology laboratories to develop diagnostic tests to identify these viruses. Nucleic acid amplification tests (NATs) that first appeared two decades ago have been developed for both conventional and emerging viruses and now form the backbone of the clinical laboratory. NATs provide fast, accurate and sensitive detection of respiratory viruses and have significantly increased our understanding of the epidemiology of these viruses. Multiplex PCR assays have been introduced recently and several commercial tests are now available. The final chapter in the evolution of respiratory virus diagnostics will be the addition of allelic discrimination and detection of single nucleotide polymorphisms associated with antiviral resistance to multiplex assays. These resistance assays together with new viral load tests will enable clinical laboratories to provide physicians with important information for optimal treatment of patients.
Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI (2005)

Lipid-rich atherosclerotic plaques are vulnerable, and their rupture can cause the formation of a platelet- and fibrin-rich thrombus leading to myocardial infarction and ischemic stroke. Although the role of plaque-based tissue factor as stimulator of blood coagulation has been recognized, it is not known whether plaques can cause thrombus formation through direct activation of platelets. We isolated lipid-rich atheromatous plaques from 60 patients with carotid stenosis and identified morphologically diverse collagen type I- and type III-positive structures in the plaques that directly stimulated adhesion, dense granule secretion, and aggregation of platelets in buffer, plasma, and blood. This material also elicited platelet-monocyte aggregation and platelet-dependent blood coagulation. Plaques exposed to flowing blood at arterial wall shear rate induced platelets to adhere to and spread on the collagenous structures, triggering subsequent thrombus formation. Plaque-induced platelet thrombus formation was observed in fully anticoagulated blood (i.e., in the absence of tissue factor-mediated coagulation). Mice platelets lacking glycoprotein VI (GPVI) were unable to adhere to atheromatous plaque or form thrombi. Human platelet thrombus formation onto plaques in flowing blood was completely blocked by GPVI inhibition with the antibody 10B12 but not affected by integrin alpha2beta1 inhibition with 6F1 mAb. Moreover, the initial platelet response, shape change, induced by plaque was blocked by GPVI inhibition but not with alpha2beta1 antagonists (6F1 mAb or GFOGER-GPP peptide). Pretreatment of plaques with collagenase or anti-collagen type I and anti-collagen type III antibodies abolished plaque-induced platelet activation. Our results indicate that morphologically diverse collagen type I- and collagen type III-containing structures in lipid-rich atherosclerotic plaques stimulate thrombus formation by activating platelet GPVI. This platelet collagen receptor, essential for plaque-induced thrombus formation, presents a promising new anti-thrombotic target for the prevention of ischemic cardiovascular diseases.
Differentiation of Infectious Bronchitis Virus Serotypes Using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism Analysis (1993)

Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to differentiate between serotypes of several infectious bronchitis virus (IBV) strains. A sequence of 1720 base pairs (bp) that contains the S1 glycoprotein gene of IBV was amplified by PCR, purified, and digested with restriction enzymes. Eleven reference IBV strains were grouped according to the RFLP patterns. The IBV Holte, Arkansas DPI, SE 17, Md 27, and Iowa 97 strains could be differentiated from the other IBV strains using the restriction enzyme HaeIII. The Beaudette, Massachusetts 41, Connecticut, and Florida 88 strains had the same HaeIII RFLP pattern but could be differentiated using XcmI and BstYI restriction enzymes. The Gray and JMK strains could not be differentiated by their RFLP patterns following digestion with 23 different restriction enzymes. Twenty-six samples (field isolates and reference strains) of IBV, previously serotypes by the virus-neutralization (VN) test in embryonating eggs, were analyzed in a blind fashion. The results using the PCR and RFLP analysis agreed with the serotype for traditional and variant IBV viruses as determined by the VN test.
Nucleotide sequence and expression of the Escherichia coli dapB gene. (1984)

The Escherichia coli dapB gene encodes dihydrodipicolinate reductase. This enzyme is part of the diaminopimelate-lysine pathway, and its synthesis is repressed by lysine. The dapB gene was cloned into pBR322 from a transducing lambda bacteriophage, its complete nucleotide sequence established, and the transcriptional start localized. The DNA sequence predicts that the dapB gene codes for a 273-amino acid polypeptide, Mr 28,798. No attenuation-type sequence can be found between the mRNA start and the coding sequence. The dapB promoter signals appear to be weak as compared to RNA polymerase consensus sequences. Nevertheless an efficient in vivo synthesis of beta-galactosidase was obtained when the lac operon was inserted in vitro in the dapB gene, downstream of the dapB regulatory signals. Further studies were performed on an in-frame gene fusion constructed in vitro between the dapB and the lacZ genes. They indicated that repression by lysine is exerted on a DNA region restricted to a 153-base pair fragment with only 102 nontranscribed nucleotides. Finally, dapB gene expression showed a gene dosage effect which suggests that it is not controlled by an element present in limiting amounts in the cell.
Prevalence of high risk genital papillomaviruses in the Belgian female population determined by fast multiplex polymerase chain reaction (1992)

Because in situ/filter hybridisation is not sensitive enough and because classical polymerase chain reaction (PCR) protocols are generally not sufficiently reproducible and specific, there is little accurate information on the prevalence of human papillomaviruses (HPV) 16, 18, and 33 infections in women without dyskaryotic changes of the cervix. In our hands, our Fast Multiplex PCR protocol has always been the most sensitive, specific, and reproducible DNA detection assay in all the microbiological and haematological applications we attempted (Vandenvelde C, Verstraete M, Van Beers D [1990]: Journal of Virological Methods 30:215-228; Vandenvelde C, Scheen R, Corazza F, Van Beers D [1991a]: Journal of Experimental and Clinical Hematology 33:293-297; Vandenvelde C, Scheen R, Van Beers D, Fondu P [1991b]: Journal of Experimental and Clinical Hematology 30:25-29). Using this new technique, cervical scrapes from 336 Belgian women attending the cervical cancer screening clinic were examined for the presence of these three high-risk genital papillomaviruses. Positive results were confirmed using another set of HPV-specific primers. Exactly one sixth of our population was found positive for one or more of these HPVs. Types 33 and 16 were significantly more prevalent than type 18. The nonparametric statistical analysis of the data suggests that some risk factors such as particular sexual habits, that are inversely related to age, must exist.
Mutation Frequencies and Antibiotic Resistance (2000)

Antibiotic resistance can be achieved by horizontal acquisition of resistance genes (carried by plasmids or transposons), by recombination of foreign DNA into the chromosome, or by mutations in different chromosomal loci ([15][1]). In studies of molecular evolutionary biology, the term mutation rate
Enzyme Immunoassay for the Identification of Hemoglobin Variants (1990)

We have prepared monospecific antibodies to Hbs D-Los Angeles, J-Baltimore, O-Arab and J-Paris-I and developed an enzyme immunoassay (ELISA) for their identification in hemolysates. Hbs in adult or cord blood hemolysates were coated to the wells of microtiter plates and reacted with the appropriate antisera followed by the detection system which contains anti-rabbit IgG/peroxidase conjugate and the substrate tetramethylbenzidine. Sixty-nine samples were tentatively considered to contain the above hemoglobin variants by isoelectrofocusing and the identity of 83% of them was confirmed by ELISA. Some of the non-reacting hemolysates were shown by amino acid sequence analysis to contain Hbs Korle-Bu, D-Ibadan, G-Copenhagen and the new variant Chandigarh. This ELISA offers specificity and simplicity for the confirmatory identification of hemoglobin variants.