gebhart/patrepeval huggingface dataset:
Mice completely suppressed for the expression of immunoglobulin kappa light chain. (1984)

Complete suppression of expression of immunoglobulin kappa light chain was achieved by injecting female mice from birth with a mixture of antisera against the mu heavy chain and kappa light chain (anti-mu and anti-kappa). Then their offspring were injected with anti-kappa from birth. This resulted in stable suppression as long as anti-kappa injections were continued. kappa light chain was not detectable either in serum or at the cellular level. The number of B cells in spleen and the concentration of immunoglobulin classes and subclasses in serum were normal. The normal levels were achieved by a compensating enhancement of lambda light chain expression. Analysis of the light chains of immunoglobulins secreted by spleen cells from suppressed mice after liposaccharide stimulation by two-dimensional gels showed lambda chain to have a limited heterogeneity. Primary responses to dinitrophenol, influenza strain A, and keyhole limpet hemocyanin were drastically affected, whereas secondary responses appeared to be quite normal, suggesting a surprisingly large potential repertoire.
Evaluation of the anti-influenza virus activities of 1,3,4-thiadiazol-2-ylcyanamide (LY217896) and its sodium salt (1990)

1,3,4-Thiadiazol-2-ylcyanamide (LY217896) and its sodium salt were shown to be effective against influenza A and B viruses in vitro and in the mouse model. In nondividing confluent MDCK cells, the 50% inhibitory concentration of LY217896 ranged from 0.37 to 1.19 micrograms/ml against various strains of influenza A virus and from 0.75 to 1.54 micrograms/ml against various strains of influenza B virus, with no apparent cytotoxicity. However, at a concentration of 0.31 microgram/ml, LY217896 inhibited the replication of dividing MDCK cells. LY217896 (9 mg/m2 of body surface area per day) administered in the diet, in the drinking water, by oral gavage, by intraperitoneal injection, or by aerosolization was well tolerated and protected CD-1 mice infected with a lethal dose of influenza A or B virus. Effective administration of the compound could be delayed for up to 96 h postinfection. Virus titer was reduced by 1 to 2 log10 units in lungs of mice given LY217896 in the drinking water. Mice treated initially with protective levels of LY217896 were resistant to a subsequent challenge of influenza virus in the absence of the compound, indicating that the animals were able to develop immunity to the initial infection. Administration of LY217896 to uninfected mice did not induce interferon-like activity or interfere with natural killer cell function. In the ferret, LY217896 was effective in preventing fever induced by influenza virus.
Regulation of FoxP3+Regulatory T Cells and Th17 Cells by Retinoids (2008)

Vitamin A has both positive and negative regulatory functions in the immune system. While vitamin A is required for normal formation of immune cells and epithelial cell barriers, vitamin A deficiency can lead to increased inflammatory responses and tissue damage. The mechanism with which vitamin A and its metabolites such as retinoids negatively regulate inflammatory responses has not been clearly defined. Recently, it has been established that retinoids promote the generation of immune-suppressive FoxP3+ regulatory T cells while they suppress the T cell differentiation into inflammatory Th17 cells in the periphery such as intestine. These novel functions of retinoids provide a potentially important immune regulatory mechanism. In this review, we discuss the functions of retinoids in the development of the FoxP3+ cells and Th17 cells, the phenotype and functions of retinoid-induced FoxP3+ T cells, and the impact of retinoid-induced FoxP3+ T cells on the immune tolerance.
Mixture density networks (1994)

Minimization of a sum-of-squares or cross-entropy error function leads to network out-puts which approximate the conditional averages of the target data, conditioned on the input vector. For classications problems, with a suitably chosen target coding scheme, these averages represent the posterior probabilities of class membership, and so can be regarded as optimal. For problems involving the prediction of continuous variables, how-ever, the conditional averages provide only a very limited description of the properties of the target variables. This is particularly true for problems in which the mapping to be learned is multi-valued, as often arises in the solution of inverse problems, since the average of several correct target values is not necessarily itself a correct value. In order to obtain a complete description of the data, for the purposes of predicting the outputs cor-responding to new input vectors, we must model the conditional probability distribution of the target data, again conditioned on the input vector. In this paper we introduce a new class of network models obtained by combining a conventional neural network with a mixture density model. The complete system is called a Mixture Density Network, and can in principle represent arbitrary conditional probability distributions in the same way that a conventional neural network can represent arbitrary functions. We demonstrate the eectiveness of Mixture Density Networks using both a toy problem and a problem involving robot inverse kinematics. 1 Previously issued as NCRG/94/4288
Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity (2010)

Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%-80% of patients. In these individuals, the function of HCV-specific CD8+ T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1-Tim-3- HCV-specific CTLs greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection. Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches.
Genome-wide profiling of adenine base editor specificity by EndoV-seq (2019)

The adenine base editor (ABE), capable of catalyzing A•T to G•C conversions, is an important gene editing toolbox. Here, we systematically evaluate genome-wide off-target deamination by ABEs using the EndoV-seq platform we developed. EndoV-seq utilizes Endonuclease V to nick the inosine-containing DNA strand of genomic DNA deaminated by ABE in vitro. The treated DNA is then whole-genome sequenced to identify off-target sites. Of the eight gRNAs we tested with ABE, 2-19 (with an average of 8.0) off-target sites are found, significantly fewer than those found for canonical Cas9 nuclease (7-320, 160.7 on average). In vivo off-target deamination is further validated through target site deep sequencing. Moreover, we demonstrated that six different ABE-gRNA complexes could be examined in a single EndoV-seq assay. Our study presents the first detection method to evaluate genome-wide off-target effects of ABE, and reveals possible similarities and differences between ABE and canonical Cas9 nuclease.
The Pfitzinger Reaction in the Synthesis of Quinoline Derivatives (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Pfitzinger Reaction in the Synthesis of Quinoline DerivativesNg. Ph. Buu-Hoi, R. Royer, Ng. D. Xuong, and P. JacquignonCite this: J. Org. Chem. 1953, 18, 9, 1209–1224Publication Date (Print):September 1, 1953Publication History Published online1 May 2002Published inissue 1 September 1953https://pubs.acs.org/doi/10.1021/jo50015a019https://doi.org/10.1021/jo50015a019research-articleACS PublicationsRequest reuse permissionsArticle Views1043Altmetric-Citations53LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin) (1991)

The transmembrane epithelial cell-cell adhesion protein E-cadherin (uvomorulin) associates via its cytoplasmic domain with three or more proteins whose structure and function are not yet established. The associated proteins, also termed catenins (Ozawa, M., Baribault, H., and Kemler, R. (1989) EMBO J. 8, 1711-1717), are of interest because they may form a link to the cytoskeleton, and/or regulate E-cadherin function. In this report immunoprecipitates of E-cadherin complexes, isolated from Xenopus laevis A6 and Madin-Darby canine kidney cell monolayers, were stringently washed to leave a single very tightly associated protein of approximately 92 kDa. We report on the 92-kDa protein's association with E-cadherin in the presence of various perturbants, its preferential dissociation from the immune complex upon exposure to mixed detergent micelles containing sodium dodecyl sulfate, and its preparative purification to homogeneity. We have additionally found that E-cadherin and its associated proteins may be easily and quantitatively extracted from both subconfluent and fully confluent cells by a variety of mild nonionic detergents made up in isotonic buffers. In contrast, such extractions at short times left most of the cytoskeletal protein fodrin in the insoluble pellet fraction. Western blots of immunoprecipitated E-cadherin complexes failed to detect the presence of fodrin, or that of the cytoskeletal proteins adducin, alpha-actinin, and vinculin. If the E-cadherin-associated protein complex interacts with known proteins of the cell cytoskeleton, such interactions are labile and/or transient.
A native plant growth promoting bacterium, Bacillus sp. B55, rescues growth performance of an ethylene-insensitive plant genotype in nature (2012)

Many plants have intimate relationships with soil microbes, which improve the plant's growth and fitness through a variety of mechanisms. Bacillus sp. isolates are natural root-associated bacteria, isolated from Nicotiana attenuata plant roots growing in native soils. A particular isolate B55, was found to have dramatic plant growth promotion (PGP) effects on wild type (WT) and transgenic plants impaired in ethylene (ET) perception (35S-etr1), the genotype from which this bacterium was first isolated. B55 not only improves N. attenuata growth under in vitro, glasshouse, and field conditions, but it also "rescues" many of the deleterious phenotypes associated with ET insensitivity. Most notably, B55 dramatically increases the growth and survival of 35S-etr1 plants under field conditions. To our knowledge, this is the first demonstration of a PGP effect in a native plant-microbe association under natural conditions. Our study demonstrates that this facultative mutualistic plant-microbe interaction should be viewed as part of the plant's extended phenotype. Possible modalities of recruitment and mechanisms of PGP are discussed.
In the Shadow of Hemagglutinin: A Growing Interest in Influenza Viral Neuraminidase and Its Role as a Vaccine Antigen (2014)

Despite the availability of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to have a significant, annual impact on the morbidity and mortality of human beings, highlighting the continued need for research in the field. Current vaccine strategies predominantly focus on raising a humoral response against hemagglutinin (HA)-the more abundant, immunodominant glycoprotein on the surface of the influenza virus. In fact, anti-HA antibodies are often neutralizing, and are used routinely to assess vaccine immunogenicity. Neuraminidase (NA), the other major glycoprotein on the surface of the influenza virus, has historically served as the target for antiviral drug therapy and is much less studied in the context of humoral immunity. Yet, the quest to discern the exact importance of NA-based protection is decades old. Also, while antibodies against the NA glycoprotein fail to prevent infection of the influenza virus, anti-NA immunity has been shown to lessen the severity of disease, decrease viral lung titers in animal models, and reduce viral shedding. Growing evidence is intimating the possible gains of including the NA antigen in vaccine design, such as expanded strain coverage and increased overall immunogenicity of the vaccine. After giving a tour of general influenza virology, this review aims to discuss the influenza A virus neuraminidase while focusing on both the historical and present literature on the use of NA as a possible vaccine antigen.
Ultrasound of the airway (2011)

Currently, the role of ultrasound (US) in anaesthesia-related airway assessment and procedural interventions is encouraging, though it is still ill defined. US can visualise anatomical structures in the supraglottic, glottic and subglottic regions. The floor of the mouth can be visualised by both transcutaneous view of the neck and also by transoral or sublinguial views. However, imaging the epiglottis can be challenging as it is suspended in air. US may detect signs suggestive of difficult intubation, but the data are limited. Other possible applications in airway management include confirmation of correct endotracheal tube placement, prediction of post-extubation stridor, evaluation of soft tissue masses in the neck prior to intubation, assessment of subglottic diameter for determination of paediatric endotracheal tube size and percutaneous dilatational tracheostomy. With development of better probes, high-resolution imaging, real-time picture and clinical experience, US has become the potential first-line noninvasive airway assessment tool in anaesthesia and intensive care practice.
The fms gene and the CSF-1 receptor. (1986)

The c-fms proto-oncogene encodes an integral transmembrane glycoprotein with tyrosine specific protein kinase activity whose properties resemble those of receptors for polypeptide growth factors. The relatively restricted expression of the feline c-fms gene in mononuclear phagocytes (peripheral blood monocytes and tissue macrophages) and their committed bone marrow progenitors suggested that c-fms encoded a receptor for a macrophage specific growth factor. We found that the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1 (M-CSF), is biochemically and immunologically related to the c-fms gene product, consistent with the hypothesis that c-fms is identical to the CSF-1 receptor gene (Sherr et al, 1985). Although the activity of CSF-1 has been defined through its action on haemopoietic cells, the c-fms gene is expressed in human placenta (Müller et al, 1983a) and in human choriocarcinoma cell lines derived from placental trophoblasts (Müller et al, 1983b). The latter cell lines exhibit binding sites for CSF-1, suggesting that this colony stimulating factor might also have an embryological role in placental development. The retroviral oncogene v-fms is a potent fibroblast transforming gene, whereas c-fms can be expressed at relatively high levels in certain normal tissues without causing neoplastic transformation. The glycoprotein encoded by v-fms is closely related to the c-fms gene product but differs at its extreme carboxy terminal end. Because v-fms, like c-fms, encodes a competent ligand binding domain, cells producing the v-fms gene product acquire the ability to bind CSF-1. Moreover, many fibroblast cell lines susceptible to transformation by v-fms produce the growth factor. Although this raises the possibility that v-fms transforms cells by an autocrine mechanism, antibodies to epitopes in the v-fms-coded ligand binding domain that interfere with CSF-1 binding, or antibodies to CSF-1 itself, do not affect the transformed phenotype. In membrane preparations, tyrosine-specific phosphorylation of the v-fms product appears to be constitutive, whereas in vitro phosphorylation of the c-fms-coded glycoprotein on tyrosine is enhanced in the presence of CSF-1. These results are most compatible with the possibility that critical alterations in the 3' coding region of the c-fms gene activate its kinase activity and unmask its latent transforming potential. An implication of these findings is that chromosomal rearrangements affecting c-fms could contribute to myeloid leukaemogenesis.
The Mechanism of Skin Tumor Promotion Caused by Phorbol Esters: Possible Involvement of Arachidonic Acid Cascade/Lipoxygenase, Protein Kinase C and Calcium/Calmodulin Systems (1989)

12-0-Tetradecanoylphorbol-13-acetate (TPA) has been used as a potent tumor promoter in mouse skin. The mechanisms of TPA actions were studied by using several types of inhibitors. TPA-caused responses in mouse skin such as skin tumor promotion, epidermal ornithine decarboxylase (ODC) induction and skin inflammation were inhibited by various lipoxygenase inhibitors of the arachidonic acid cascade. Lipoxygenase inhibitors also inhibited TPA-caused ODC induction in isolated epidermal cells or cultured epidermal cells. Therefore, it is possible that these drugs inhibit TPA-caused ODC induction in mouse skin by directly acting on epidermal cells. TPA actions were also inhibited by either protein kinase C inhibitors, calmodulin antagonists or calcium blockers. These results suggest that arachidonic acid/lipoxygenase, protein kinase C and calcium-calmodulin systems play essential roles in the mechanism of tumor promotion by TPA.
Nanocages Derived from Shell Cross-Linked Micelle Templates (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNanocages Derived from Shell Cross-Linked Micelle TemplatesHaiyong Huang, Edward E. Remsen, Tomasz Kowalewski, and Karen L. WooleyView Author Information Department of Chemistry, Washington University One Brookings Drive, St. Louis, Missouri 63130 Monsanto Company, 800 N. Lindbergh Boulevard, St. Louis, Missouri 63167 Cite this: J. Am. Chem. Soc. 1999, 121, 15, 3805–3806Publication Date (Web):April 3, 1999Publication History Received14 October 1998Published online3 April 1999Published inissue 1 April 1999https://pubs.acs.org/doi/10.1021/ja983610whttps://doi.org/10.1021/ja983610wrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views3877Altmetric-Citations542LEARN 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 optionsGet e-Alertsclose SUBJECTS:Hollow structures,Micelles,Nanoparticles,Polymers,Transmission electron microscopy Get e-Alerts
Thermoelectricity in Semiconductor Nanostructures (2004)

Thermoelectrics are devices that convert heat to electricity directly, or vice versa. To be technologically useful, thermoelectric materials with high efficiency must be found, along with better tools to understand them. In his Perspective,
 Majumdar
 discusses the reports by
 Hsu
 et al .
 and
 Lyeo
 et al .
 that tackle these issues. Hsu
 et al . have found a new bulk material that exhibits a so-called figure of merit with a value around 2, which is an encouraging step on the road to materials that could compete with conventional thermodynamic devices such as power generators and refrigerators. Lyeo
 et al . report on a new technique for measuring thermoelectric properties over nanometer scales. The interdisciplinary combination of thermoelectric research with microelectronics and nanotechnology, Majumdar argues, will have a positive impact on both fields.
Phototriggered, Metal-Free Continuous Assembly of Polymers for the Fabrication of Ultrathin Films (2012)

A facile and metal-free thin film fabrication technology based on the photoinduced continuous assembly of polymers (photoCAP) is described. The efficiency and versatility of this method is demonstrated by the formation of crosslinked and surface-confined nanoengineered thin films, in the form of surface coatings and hollow polymer capsules.
CD20 deficiency in humans results in impaired T cell–independent antibody responses (2009)

CD20 was the first B cell differentiation antigen identified, and CD20-specific mAbs are commonly used for the treatment of B cell malignancies and autoantibody-mediated autoimmune diseases. Despite this the role of CD20 in human B cell physiology has remained elusive. We describe here a juvenile patient with CD20 deficiency due to a homozygous mutation in a splice junction of the CD20 gene (also known as MS4A1) that results in "cryptic" splicing and nonfunctional mRNA species. Analysis of this patient has led us to conclude that CD20 has a central role in the generation of T cell-independent (TI) antibody responses. Key evidence to support this conclusion was provided by the observation that although antigen-independent B cells developed normally in the absence of CD20 expression, antibody formation, particularly after vaccination with TI antigens, was strongly impaired in the patient. Consistent with this, TI antipolysaccharide B cell responses were severely impeded in CD20-deficient mice. Our study therefore identifies what we believe to be a novel type of humoral immunodeficiency caused by CD20 deficiency and characterized by normal development of antigen-independent B cells, along with a reduced capacity to mount proper antibody responses.