gebhart/patrepeval huggingface dataset:
The Trimera mouse: a system for generating human monoclonal antibodies and modeling human diseases. (2002)

A Trimera mouse is constructed through a three-step process. Firstly, a normal mouse host is rendered immuno-incompetent by a lethal split-dose total body irradiation. Secondly, the myeloid and erythroid lineages are reconstituted by transplantation of bone marrow cells from a genetically immune-deficient mouse donor. Thirdly. the resulting preconditioned mouse is transplanted with human cells or tissues that can be maintained in the foreign, yet supporting, environment for a considerable period of time. Immunization of Trimera mice, engrafted with human immune cells, induces a strong human immune response, thereby enabling generation of human therapeutic monoclonal antibodies (mAbs) via hybridoma technology. Transplantation of infected human tissue into the preconditioned mice results in the creation of Trimera mouse models for human diseases.
Liver Disease in Alpha-1 Antitrypsin Deficiency: Current Understanding and Future Therapy (2013)

Alpha-1 antitrypsin Deficiency (AATD) is a common, but under recognized metabolic genetic disease. Although many mutations in the alpha-1 antitrypsin (AAT) gene are described, the Z variant is the allele overwhelmingly associated with liver disease. PI*ZZ homozygotes occur in approximately 1 in 2,000-5,000 births in North American and European populations. The AAT protein is synthesized in large quantities by the liver, and then secreted into serum. Its physiologic function is to inhibit neutrophil proteases in order to protect host tissues from non-specific injury during periods of inflammation. The mutant Z gene of AAT directs the synthesis of a mutant protein which folds abnormally during biogenesis in the endoplasmic reticulum of hepatocytes and is retained intracellularly, rather than efficiently secreted. Intracellular proteolysis pathways, including the proteasome and autophagy, are activated as a response to the intracellular burden of misfolded protein. The lack of circulating anti-protease activity leaves the lung vulnerable to injury and the development of emphysema. The intracellular accumulation of AAT mutant Z protein within hepatocytes can cause liver injury, cirrhosis and hepatocellular carcinoma by triggering a cascade of chronic hepatocellular apoptosis, regeneration, and end organ injury. There is no specific treatment for PI*ZZ associated liver disease, other than standard liver supportive care and liver transplantation. There is a high degree of variability in the clinical manifestations among PI*ZZ homozygous patients, suggesting a strong influence of as yet poorly characterized, genetic and environmental disease modifiers. Studies of the processes of intracellular injury have led to a new era of rational therapeutic development.
Generation of Plasma Cells From Peripheral Blood Memory B Cells: Synergistic Effect of Interleukin-10 and CD27/CD70 Interaction (1998)

B cells can differentiate into the antibody-secreting cells, plasma cells, whereas the crucial signals that positively control the entry into the pathway to plasma cells have been unclear. Triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). Differentiation into plasma cells by a combination of IL-10 and CD70 transfectants occurred in CD27+ B cells but not in CD27− B cells. Moreover, addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced differentiation into plasma cells. In the presence of only IL-2, IL-4, or IL-6, CD70 transfectants did not promote differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B-cell pool from peripheral blood B cells primarily activated by IL-2, IL-10, and anti-CD40 monoclonal antibody (MoAb). Finally, CD27 signaling also rescued B cells from IL-10–mediated apoptosis. These data demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10–mediated promotion of apoptosis and to direct the differentiation of CD27+ memory B cells toward plasma cells in cooperation with IL-10.
Effects of HTS Tape Arrangements on AC Loss in Self-Shielding DC HTS Cable With AC Ripple Current (2016)

Critical current and ac loss of high-temperature superconducting (HTS) tapes are two important factors for the application of ac HTS power cables. Generally, the current in the dc HTS cable is a combination of main dc current and ac ripple current due to the use of rectifier. The ac ripple current distribution without proper adjusting would be nonuniform in each layer especially when the dc HTS cable layer increases; it may lead to high ac loss and poor transmission capacity. In order to understand the ac ripple current sharing among dc HTS cable layers, the inductance matrix of the cable layers was deduced based on the geometry configuration of a self-shielding dc HTS cable. In this paper, in addition to the uniform current design principle, a self-shielding dc HTS cable is also designed with the HTS tape arrangements of each layer optimized by taking the ratios of ac ripple current amplitude to critical current in each layer as equal for minimizing the ac loss. According to the design configuration and deduced inductance matrix, current in each layer and ac loss are calculated. The results show that it is necessary to use the optimized design in the dc HTS cable design and the equal ratio design is better than the uniform current design.
Mapping bovine herpesvirus type 1 latency-related RNA in trigeminal ganglia of latently infected rabbits (1987)

Here we have used the bovine herpesvirus type 1 (BHV-1) rabbit model together with in situ nucleic acid hybridization to identify and map viral RNA present in latently infected neurons. Radioactively labeled cloned HindIII fragments representing most of the BHV-1 genome (Cooper strain) were individually hybridized to sections of trigeminal ganglia taken from rabbits during acute and latent stages of infection. Whereas all viral genomic fragments hybridized to lytically infected tissue culture cells and to acutely infected ganglia, only HindIII fragment D (map units 0.734 to 0.842) hybridized to latently infected ganglionic neurons. Additional in situ hybridization experiments using subcloned fragments of HindIII-D further mapped the latency-related viral RNA to a 1.9-kilobase region (map units 0.734 to 0.748) of the viral genome. These results indicate that BHV-1 gene transcription is restricted during the latent phase of infection; further, they suggest that specific viral transcription may be involved in establishment or maintenance of latent BHV-1 infection.
Energy Efficient Neural Stimulation: Coupling Circuit Design and Membrane Biophysics (2012)

The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.
Neosporosis as a cause of equine protozoal myeloencephalitis (1996)

Neosporosis was diagnosed in an 11-year-old Quarter Horse gelding with clinical signs and diagnostic test results compatible with equine protozoal myeloencephalitis (EPM). Presumptive postmortem diagnosis of EPM attributable to Sarcocystis neurona infection is generally made on the basis of detecting an antibody titer to S neurona in the CSF or characteristic histologic lesions, even when parasites have not been specifically identified. Neosporosis was confirmed in the horse described here by use of immunohistochemical examination, in vitro culturing, and ultrastructural and molecular characterization of parasites from infected tissues. Antibody testing of serum and CSF samples indicated that Neospora-specific anti-bodies can react with S neurona proteins on western blot analysis. The confirmation that neosporosis in horses can mimic EPM emphasizes the need to broaden the etiologic definition of EPM beyond infections exclusively attributable to S neurona.
Elastin Degradation by Matrix Metalloproteinases (1997)

Insoluble elastin was used as a substrate to characterize the peptide bond specificities of human (HME) and mouse macrophage elastase (MME) and to compare these enzymes with other mammalian metalloproteinases and serine elastases. New amino termini detected by protein sequence analysis in insoluble elastin following proteolytic digestion reveal the P'1 residues in the carboxyl-terminal direction from the scissile bond. The relative proportion of each amino acid in this position reflects the proteolytic preference of the elastolytic enzyme. The predominant amino acids detected by protein sequence analysis following cleavage of insoluble elastin with HME, MME, and 92-kDa gelatinase were Leu, Ile, Ala, Gly, and Val. HME and MME were similar in their substrate specificity and showed a stronger preference for Leu/Ile than did the 92-kDa enzyme. Fibroblast collagenase showed no activity toward elastin. The amino acid residues detected in insoluble elastin following hydrolysis with porcine pancreatic elastase and human neutrophil elastase were predominantly Gly and Ala, with lesser amounts of Val, Phe, Ile, and Leu. There were interesting specificity differences between the two enzymes, however. For both the serine and matrix metalloproteinases, catalysis of peptide bond cleavage in insoluble elastin was characterized by temperature effects and water requirements typical of common enzyme-catalyzed reactions, even those involving soluble substrates. In contrast to what has been observed for collagen, the energy requirements for elastolysis were not extraordinary, consistent with cleavage sites in elastin being readily accessible to enzymatic attack.
Immunology, immunopathology & immunity (1996)

Part I. Immunology. Introduction to Immunity. Immune System I: Cells and Vessels. Immune System II: Organs and Development. Antibodies, Immunoglobulins, and Receptors. Antigen Recognition and Processing. Thymic Selection of the T-Cell Repertoire. Cellular Interactions and The Immune Response. Acute Inflammation. Chronic Inflammation and Wound Healing. Clearance of Inflammatory Products. Part II. Immunopathology. A. Immunopathologic Mechanisms. Inactivation/Activation. Cytotoxic/Cytolytic. Immune Complex. Atopic/Anaphylactic. T-Cell Cytotoxicity. Delayed Hypersensitivity. Granulomatous Diseases. Interplay of Inflammatory and Immunological Mechanisms. B. Immune Disorders. Drug Allergy. Immune Skin Diseases. Autoimmune Diseases I: Tolerance and Cell- Mediated Diseases. Autoimmune Diseases II: Connective Tissue Diseases. Transplantation. Lymphoproliferative Diseases. Part III. Immunity. Immune Resistance to Infection. Vaccination. Immune Deficiency Diseases. Immunomodulation/Designing the Immune Response. Immunology of AIDS. Tumour Immunity. Appendices: Clinical Immunoligic Tests. Cluster Designations.
A Combined Biological and Enzymatic Amplification (BIO-PCR) Technique to DetectPseudomonas syringaepv.phaseolicolain Bean Seed Extracts (1995)

A polymerase chain reaction (PCR) method, hereafter referred to as BIO-PCR, that combines biological and enzymatic amplification of PCR targets and simplified procedures for sample processing is described for the detection of Pseudomonas syringae pv. phaseolicola in bean seed extracts. Seeds are soaked overnight following standard protocols and aliquots of the extracts are plated onto a general agar medium. After 45-48 hr of incubation, the plates are washed with water to remove bacterial cells and aliquots of a pooled washing are subjected to two consecutive rounds of PCR, without prior DNA extraction, using «nested» pairs of primers designed to amplify a segment of the organism's tox (phaseolotoxin) gene region. Positive detection was reproducibly obtained at near-limit concentrations of the pathogen in the seed wash. Advantages of BIO-PCR over existing PCR techniques include the elimination of false positives resulting from the presence of dead cells that may be present in the seed, elimination of false negatives due to potential PCR inhibitors in seed extracts, increased sensitivity of detection, and no need for DNA extraction prior to amplification. Accordingly, BIO-PCR should prove useful for routine detection of other bacterial pathogens of quarantine importance. The primers detected some nontoxigenic strains of the pathogen, which evidently contain part of or the entire tox gene cluster
Stereochemical comparison of nebivolol with other β‐blockers (2007)

beta-Blockers are widely used in the treatment of cardiovascular disease and act by antagonizing the effects of adrenaline (epinephrine) and noradrenaline (norepinephrine) on beta-adrenergic receptors. All beta-blockers currently used in the treatment of cardiovascular disease contain at least one chiral center and, while most are marketed as racemates, their cardiac antihypertensive activity generally resides in the S-enantiomer. Nebivolol is a third generation beta-blocker that is highly selective for the beta(1)-adrenoceptor. The nebivolol molecule contains four chiral centers and is marketed as a racemate of (+)-nebivolol (SRRR-configuration) and (-)-nebivolol (RSSS-configuration). Nebivolol differs from all other beta-blockers with a hydroxypropanolamine substructure in that its cardiac antihypertensive activity resides in the R-enantiomer at the hydroxy group, whereas all other beta-blockers have antihypertensive activity in the S-enantiomer. Two of the four chiral centers in nebivolol are part of a ring structure and the increased rigidity of this structure may be related to nebivolol's divergence from the standard pharmacophore model of beta-blockers.
Augmented indoles (2006)

The indole ring presents a good platform for synthesis because of its nucleophilic capacity at C3, to a lesser extent at C2, and also through the indole anion at N1. The development of new indoles with strategically placed methoxy groups at C4 and C6, or C5 and C7, provides even better platforms not only through increased general activation, but also through specific activation at C7 and C4 respectively. As a result of this multi-faceted activity, it is possible to generate a variety of additional rings fused to the indole platform. This rather general strategy of molecular augmentation leads to new types of indole structures, some of which bear resemblance to natural indole alkaloids. A selection of examples is presented.
Abstract 1344: TGFß, an inflammation and immune suppressor in tumor microenvironment and progression (2010)

Abstract Alterations in TGFβ signaling have significant effects on tumor initiation and progression. TGFβ functions both as a tumor suppressor and as a tumor promoter. Most work so far to dissect mechanisms underlying this dual role of TGFβ has been largely focused on differential regulation of signaling pathways by tumor autonomous TGFβ signaling. Studies from our lab demonstrate that TGFβ significantly regulate inflammation in tumor microenvironment and host immune response. When TGFβ R2 receptor is deleted in mammary cancer epithelial cells, there was an increased inflammation and recruitment of Gr-1+CD11b+ myeloid cells, which leads to increased tumor invasion and metastasis. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGFβ1 and metalloproteinase activity in tumors with Tgfbr2 deletion. Interestingly, Tumor-infiltrating Gr-1+CD11b+ cells exhibited significant elevated TGFß signaling including increased expression of RI and RII receptor, TGFß1 and TGFß3 ligands, as well as latent transforming growth factor ß binding protein when compared with normal myeloid cells. Genetic deletion of Tgfbr2 in myeloid cells significantly attenuated 4T1 breast carcinoma tumor growth and metastasis. This is accompanied with significantly increased IFNγ production in the lungs of tumor bearing mice. These data suggest that TGFß, the tumor suppressor, also functions as an inflammation and immune suppressor. TGFß signaling in host derived myeloid cells is an important mediator in tumor immune surveillance. This new understanding of TGFß in inflammation and immune response in the interface of tumor and host may provide insight information for TGFß switch from a tumor suppressor to a tumor promoter. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1344.
Measuring the shape and volume of an above-knee stump (1988)

A set of design criteria for sensing the shape of an above-knee (AK) stump is presented and used as the basis for evaluating various shape sensing technologies. A mechanical probe type shape sensing system is described and its use in quantifying the external shape of the AK stump is discussed as it relates to generating a grid for finite element analysis in CAD/CAM studies and comparing the segmental volumes of the loaded and unloaded stump. This study also discusses a method that uses circumferential measurements to compute total and incremental volumes of the stump.
[The pathogenesis of discogenic low back pain]. (2004)

Findings indicate that the strip zone of granulation tissue with extensive innervation in the posterior part of the painful disc is the original site of the pain of discography and the discogenic low back pain. The strip zone of granulation tissue might originate from the injury and subsequent reparation of the margin of annulus fibrosus. The difference of the aging disc and painful disc which can not be differed each other on MRI is the formation of the strip zone of granulation tissue along tear histologically in posterior part of the painful disc.
ChemInform Abstract: Metalation of Diazines. Part 4. Lithiation of sym‐Disubstituted Pyrazines. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The Candidate Region Approach to the Genetics of Asthma and Allergy (1997)

To date, the strongest linkage claims for genes underlying asthma and atopy have been for chromosomes 5 and 11. Chromosome 5q contains the cytokine cluster and the beta2 adrenoceptor, and the beta chain of the high-affinity IgE receptor (FCepsilonRI-beta) is encoded on chromosome 11q13. We have attempted to replicate these findings in two distinct sample populations from the United Kingdom. Allelic associations were identified in both regions, but there was no significant evidence for linkage. Although we could not substantiate the existence of the nucleotide changes reported within exon 6 of the FCepsilonRI-beta gene, an amino acid substitution in exon 7 was strongly linked to asthma and atopy. We have also identified positive linkage and allelic associations to several markers on chromosome 12q in both our UK populations. Independent evidence from another study also supports linkage to 12q, so although our data could not confirm linkage to chromosomes 5 or 11, we have identified an additional region of the genome that could be important for the genetic predisposition to asthma and atopy.
Demonstration of low temperature 3D sequential FDSOI integration down to 50 nm gate length (2011)

For the first time, 3D sequential integration is demonstrated down to L G =50nm. Molecular bonding is used to design a perfect a top active layer (thickness control, cristallinity) and a low Thermal Budget (TB) top FET (600°C) has been developed for bottom FET preservation. We demonstrate that this integration is viable for bottom and top MOSFETs with advanced L G . Additionally the low TB process compared to its high temperature counterpart translates in worthy advantages in terms of gate stack: 3A EOT decrease, improved insulating properties. We demonstrate also the smallest Inter-Layer-Dielectric (ILD) thickness down to 23 nm, paving the way to ultra dense and robust SRAMs.
A racemic protein (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA racemic proteinLaura E. Zawadzke and Jeremy M. BergCite this: J. Am. Chem. Soc. 1992, 114, 10, 4002–4003Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/ja00036a073https://doi.org/10.1021/ja00036a073research-articleACS PublicationsRequest reuse permissionsArticle Views427Altmetric-Citations84LEARN 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