gebhart/patrepeval huggingface dataset:
OX40/OX40L axis: not a friend in autoimmunity (2015)

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance toward nuclear components, and multiple organs such as kidney, brain, vessels or skin are affected. SLE presents a waxing and waning course, rendering its outcome hardly predictable. A better understanding of human SLE pathogenesis is direly needed because only few effective treatments are available. While the precise immunological events that trigger the onset of SLE remain unknown, chronic activation of the dendritic cell (DC) system plays an important role for the activation of autoreactive T and B lymphocytes while overwhelming natural regulatory mechanisms. Generation of autoantibodies targeting broad repertoire of self antigens and formation of immune complexes are the hallmark of SLE. Central to antibody production is the interactions between CD4+ T cells and B cells particularly in germinal centers (GCs), the site of affinity maturation and the subsequent generation of memory B cells and long-lived plasma cells. In SLE, a majority of IgG class autoantibody-producing B cells are somatically mutated indicating that they are derived from GCs [1]. Consistently, recent data in humans and mice show that overrepresentation of T follicular helper cells (Tfh), a CD4+ T cell subset specialized in helping B cells in GCs, is associated with autoimmunity including SLE [2]. However, the mechanism that leads to the exaggerated Tfh response in SLE was largely unknown. Our recent study demonstrated that the OX40-OX40 ligand (OX40L) axis contributes to the lupus pathogenesis in this context [3].
Evaluation of the reported rates of hypersensitivity reactions associated with iron dextran and ferric carboxymaltose based on global data from VigiBase™ and IQVIA™ MIDAS® over a ten-year period from 2008 to 2017 (2020)

<b>Objectives</b>: It is hypothesized that the risk of hypersensitivity reactions (HSRs) may be lower with ferric carboxymaltose than iron dextran because of its non-dextran carbohydrate moiety. This study compares the risk of HSRs between iron dextran and ferric carboxymaltose.<b>Methods</b>: This was a retrospective pharmacoepidemiological study with a case-population design covering 2008-2017. Global exposure data were estimated using IQVIA™ sales data. Spontaneously reported HSR data were retrieved from the World Health Organization database (VigiBase™) using different search criteria including: the Standardized MedDRA® Query (SMQ) 'Anaphylactic reaction'; type I-IV HSR terms; narrow terms for anaphylactic/anaphylactoid reactions; and cases with a fatal outcome.<b>Results</b>: Total exposure in 100 mg doses was 117.3 million for iron dextran and 84.2 million for ferric carboxymaltose. The relative risk (with 95% confidence interval) for ferric carboxymaltose versus iron dextran was 4.18 (3.88-4.50) for SMQ Anaphylactic reaction; 12.9 (9.90-16.7) for type I-IV HSRs; 1.72 (1.45-2.04) for anaphylactic/anaphylactoid reactions; and 1.92 (1.24-2.99) for death.<b>Conclusion</b>: The risk of spontaneously reported HSRs was consistently higher with ferric carboxy-maltose than with iron dextran over the period 2008-2017. Thus, this study does not support that dextran-free intravenous irons are associated with fewer HSRs than iron dextran.
Regulation of expression of human immunodeficiency virus. (1990)

Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS), encodes regulatory factors necessary for its expression. The study of these factors clearly indicates the importance and complexity of post-trascriptional processes in regulating gene expression. Two regulatory proteins, Tat and Rev, are necessary for viral replication. These small nuclear proteins accumulate primarily in the nucleoli and act on HIV via sequence-specific elements found on the viral RNA. Both the Tat responsive element (TAR) and the Rev responsive element (RRE) map within regions of strong RNA secondary structure. While all viral mRNAs contain TAR, only the mRNAs producing HIV structural proteins contain RRE. Tat increases the levels of all viral mRNAs. Its function is complex and involves transcriptional and possibly post-transcriptional steps. Rev promotes the transport of viral mRNAs containing RRE from the nucleus to the cytoplasm and increases the half-life of these viral mRNAs. A third factor, Nef, is a cytoplasmic myristylated protein that has been proposed to down-regulate virus expression. These factors are integrated in a feedback regulatory network that dictates the balanced expression of viral components. The study of HIV expression in human cells will advance our understanding of the mechanisms related to the pathogenicity of HIV. This knowledge may also lead to novel diagnostic and therapeutic approaches to combat AIDS.
Comparison of the Flow Properties of Aqueous Suspension Corticosteroid Nasal Sprays Under Differing Sampling Conditions (2003)

Many aqueous suspension corticosteroid nasal sprays become less viscous when shaken and sprayed, then return to a more viscous state after application. This time-dependent, reversible loss of viscosity under shear (e.g., shaking or spraying) can be quantified in the rheological property of thixotropy. The flow properties of 5 corticosteroid nasal sprays were measured over a range of shear rates. The formulations tested included Nasonex, Vancenase AQ, Nasacort AQ, Rhinocort Aqua, and Flonase. The yield stress values, as well as an estimate of thixotropy, were compared by using three different sampling techniques, including one that simulated patient use (shaking for 30 sec, spraying, and immediately transferring the sample to the rheometer). The rheological properties of all products indicated that when initially shaken and dispensed, they flowed more freely, followed by recovery of viscosity that would likely inhibit the suspensions from flowing out of the nasal cavity. Under all three tested conditions, Nasonex exhibited the highest yield stress, the largest apparent initial and final viscosities, and the highest apparent thixotropy. The study protocol that simulated patient-use conditions produced the following rank order of measured thixotropy: Nasonex > Flonase > Vancenase AQ > Rhinocort Aqua > Nasacort AQ. The thixotropy of Nasonex was 3.4 to 21.4 times greater and the final viscosity was 3.2 to 17.4 times greater than the values of the other tested products.
Characterization of Lymphoma-Derived Cell Lines: Comparison of Cell Lines Positive and Negative for Epstein-Barr Virus Nuclear Antigen. I. Physical, Cytogenetic, and Growth Characteristics (1980)

Sixteen lymphoid cell lines were derived from patients with undifferentiated lymphoma of Burkitt's or non-Burkitt's type. They were obtained directly from tumor biopsies, from serous effusions, or from bone marrow. In 10 of the cell lines, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) was undetectable; the remaining 6 lines were EBNA-positive (EB-pos). Of the 16 lines, 15 were aneuploid, with detectable chromosome "14q+ markers (11 had +8;14 translocations). These 15 lines, which included the EBNA-negative (EB-neg) lines, were believed to be of tumor cell origin. The remaining line consisted predominantly of diploid cells derived from normal lymphocytes, but some cells of tumor origin were present. Four EB-pos cell lines derived from EB-neg tumors had an aneuploid karyotype consistent with an origin from tumor cells (including no.8;14 translocation in two), which suggested that either tumor cells were infected with EBV in vitro or a tiny fraction of EB-pos tumor cells (or potential tumor cells) present in vivo gave rise to the predominant cell of the line. EB-neg B-cell lines and EB-pos cell lines established from undifferentiated lymphomas differed greatly. EB-neg lines had consistently smaller electronic mean cell volumes and narrow-angle light scatter than did EB-pos lines. This finding correlated with a lower nuclear:cytoplasmic ratio in EB-pos lines. EB-neg lines also had higher saturation cell densities than did EB-pos lines under standard culture conditions. The data indicate either that EBV influences the morphologic and physiologic characteristics of lymphoid cell lines or that EB-neg B-cell lines and EB-pos cell lines are derived ultimately from different lymphocyte subpopulations or that both may apply.
Optimization of the production of knock-in alleles by CRISPR/Cas9 microinjection into the mouse zygote (2017)

Microinjection of the CRISPR/Cas9 system in zygotes is an efficient and comparatively fast method to generate genetically modified mice. So far, only few knock-in mice have been generated using this approach, and because no systematic study has been performed, parameters controlling the efficacy of CRISPR/Cas9-mediated targeted insertion are not fully established. Here, we evaluated the effect of several parameters on knock-in efficiency changing only one variable at a time. We found that knock-in efficiency was dependent on injected Cas9 mRNA and single-guide RNA concentrations and that cytoplasmic injection resulted in more genotypic complexity compared to pronuclear injection. Our results also indicated that injection into the pronucleus compared to the cytoplasm is preferable to generate knock-in alleles with an oligonucleotide or a circular plasmid. Finally, we showed that Cas9D10A nickase variant was less efficient than wild-type Cas9 for generating knock-in alleles and caused a higher rate of mosaicism. Thus, our study provides valuable information that will help to improve the future production of precise genetic modifications in mice.
Shaw, Clifford (2013)

Abstract Clifford Shaw was best known for his work at the University of Chicago and for his development of the Chicago Area Project. Shaw in collaboration with Henry McKay further explored social disorganization by developing what was perhaps the first crime‐mapping analysis. Their work explained delinquency rates in Chicago using the Concentric Zone Model and discovered the highest level of offending in transition areas marked by poverty.
Future of simulation optimization (2001)

The combination of simulation and optimization, essentially unheard of in practice a decade ago, is much more accessible today, thanks in large part to the development of commercial optimization software designed for use with existing simulation packages. Despite this growth, untapped applications abound. This panel, which includes developers of simulation-optimization packages, will discuss this untapped potential, barriers to broader applicability, and approaches for overcoming these barriers. This paper starts off with a brief introduction by the panel’s organizer, followed by position statements from the panelists.
Efficient amplification of melanoma-specific CD8+ T cells using artificial antigen presenting complex (2006)

In vitro large amplification of tumor-specific cytotoxic T lymphocytes (CTLs) and adoptive transfer of these cells is one of the most promising approaches to treat malignant diseases in which an effective immune response is not achieved by active immunization. However, generating sufficient numbers of tumor-specific CTLs stimulated with autologous antigen presenting cells (APCs) in vitro is one of the most problematic steps in the adoptive cell transfer (ACT) therapy. To circumvent this problem, we have developed an artificial antigen presenting complex (aAPCs) using MHC class I molecules loaded with a melanoma-specific TRP-2 peptide epitope. Our results show that TRP-2-specific CD8+ T cells elicited by immunization with recombinant adenovirus expressing the mini-gene epitope are efficiently stimulated and amplified in vitro to a greater extent by aAPCs than by natural splenic APCs. These aAPC-induced CTLs recognized endogenously processed antigens present on B16F10 melanoma cells. Efficient stimulation and proliferation of antigen- specific T cells was also confirmed using ovalbumin peptide-loaded aAPCs and OT-I TCR transgenic cells. These results demonstrate that prior in vivo immunization, which increases the precursor frequency, simplifies posterior expansion of tumor- specific CD8+ T cells, and aAPCs is superior to autologous APC for in vitro amplification. This "prime and expand" regimen can be an alternative method for large amplification of rare tumor-specific CTLs and aAPCs should be a useful tool for ACT immunotherapy.
An interactive region-of-interest video streaming system for online lecture viewing (2010)

ClassX is an interactive online lecture viewing system developed at Stanford University. Unlike existing solutions that restrict the user to watch only a pre-defined view, ClassX allows interactive pan/tilt/zoom while watching the video. The interactive video streaming paradigm avoids sending the entire field-of-view in the recorded high resolution, thus reducing the required data rate. To alleviate the navigation burden on the part of the online viewer, ClassX offers automatic tracking of the lecturer. ClassX also employs slide recognition technology, which allows automatic synchronization of digital presentation slides with those appearing in the lecture video. This paper presents a design overview of the ClassX system and the evaluation results of a 3-month pilot deployment at Stanford University. The results demonstrate that our system is a low-cost, efficient and pragmatic solution to interactive online lecture viewing.
Dissection of the Bifunctional Escherichia coli N-Acetylglucosamine-1-phosphate Uridyltransferase Enzyme into Autonomously Functional Domains and Evidence That Trimerization Is Absolutely Required for Glucosamine-1-phosphate Acetyltransferase Activity and Cell Growth (2001)

The bifunctional N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) enzyme catalyzes both the acetylation of glucosamine 1-phosphate and the uridylation of N-acetylglucosamine 1-phosphate, two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis in bacteria. In our previous work describing its initial characterization in Escherichia coli, we proposed that the 456-amino acid (50.1 kDa) protein might possess separate uridyltransferase (N-terminal) and acetyltransferase (C-terminal) domains. In the present study, we confirm this hypothesis by expression of the two independently folding and functional domains. A fragment containing the N-terminal 331 amino acids (Tr331, 37.1 kDa) has uridyltransferase activity only, with steady-state kinetic parameters similar to the full-length protein. Further deletion of 80 amino acid residues at the C terminus results in a 250-amino acid fragment (28.6 kDa) still exhibiting significant uridyltransferase activity. Conversely, a fragment containing the 233 C-terminal amino acids (24.7 kDa) exhibits acetyltransferase activity exclusively. None of these individual domains could complement a chromosomal glmU mutation, indicating that each of the two activities is essential for cell viability. Analysis of truncated GlmU proteins by gel filtration further localizes regions of the protein involved in its trimeric organization. Interestingly, overproduction of the truncated Tr331 protein in a wild-type strain results in a rapid depletion of endogenous acetyltransferase activity, an arrest of peptidoglycan synthesis and cell lysis. It is shown that the acetyltransferase activity of the full-length protein is abolished once trapped within heterotrimers formed in presence of the truncated protein, suggesting that this enzyme activity absolutely requires a trimeric organization and that the catalytic site involves regions of contact between adjacent monomers. Data are discussed in connection with the recently obtained crystal structure of the truncated Tr331 protein.
Analysis of Associations Between Major Histocompatibility Complex (BoLA) Class I Haplotypes and Subclinical Mastitis of Dairy Cows (1995)

The associations between BoLA class I haplotypes and subclinical mastitis were investigated using information on 333 cows from three different breeds and crossbreeds from 14 dairy herds in Denmark. Somatic cell count and bacteriological status were used as markers for subclinical mastitis. Associations between BoLA class I haplotypes and IMI status were also determined. The association between BoLA class I haplotypes and subclinical mastitis was weak. The A10(W50), A11, A12(A30), A16, A19(A6), A21, A26, and A31(A30) alleles were associated with different markers of subclinical mastitis. Susceptibility or resistance to the two bacteria categories was associated with different alleles. This study indicated that BoLA antigens may be involved in resistance to mastitis and that resistance may be specific for a particular pathogen.
High serum levels of B‐lymphocyte stimulator are associated with clinical–pathological features and outcome in classical Hodgkin lymphoma (2007)

B-lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed-Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinical-pathological features and outcomes. Enzyme-linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean +/- standard error 4493.9 +/- 264.9 pg/ml vs. 2687.0 +/- 200.9 pg/ml; P < 0.0001). Levels above the median value (4242.0 pg/ml) were associated with age > or = 45 years (P = 0.042), advanced stages of disease (P = 0.005), systemic symptoms (P = 0.014) and extranodal involvement (P = 0.009). Five-year failure-free survival (FFS) of patients with sBLyS below or equal to median levels was 88.6% as compared to 65.1% of those with levels above the median (P = 0.009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0.046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target.
Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. (2006)

This work provides insight into the evolutionary history for the PE and PPE gene families of the mycobacteria, linking the expansion of these families to the duplications of the ESAT-6 (esx) gene cluster regions, and showing that they are composed of subgroups with distinct evolutionary (and possibly functional) differences.
Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? (2009)

Multipotent mesenchymal stromal cells (MSCs) have raised interest mainly because of cartilage/bone differentiation potential which is now partly eclipsed by their capacity to counteract inflammation and suppress host immune responses as well as to prevent fibrosis. MSCs have been identified within joint tissues including synovium, cartilage, subchondral bone, periosteum or adipose tissue. They are characterized by their phenotype and their ability to differentiate into three lineages, chondrocytes, osteoblasts and adipocytes. MSCs have also paracrine effects through the secretion of a number of cytokines and growth factors. This may explain the trophic effects that may be of therapeutic value for rheumatic diseases including OA and RA. On the other hand, MSCs have been associated with tumour growth. MSCs migrate to the tumour stroma, express chemokines involved in the attraction of carcinoma cells in metastasis. Indeed, the aim of this review is not only to focus on new potential therapeutic applications in osteo-articular diseases, but also to assess the potential risk of MSC-based cell therapy.
suPAR as a prognostic biomarker in sepsis (2012)

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis.
Escherichia coli Electrotransformation (2003)

Electroporation is now being used to transfer into cells a variety of macromolecules, including DNA, RNA, protein, fluorescent dyes, and some chemotherapeutic agents. With electrotransformation, as many as 80% of the cells receive exogenous DNA (). Chemical and natural methods of DNA transfer into bacteria are also effective for transforming bacteria, but they are more cumbersome and time-consuming, and generally less efficient than electrotransformation.
Genetic Adjuvants in Replicating Single-Cycle Adenovirus Vectors Amplify Systemic and Mucosal Immune Responses against HIV-1 Envelope (2020)

Most infections occur at mucosal surfaces. Providing a barrier of protection at these surfaces may be a useful strategy to combat the earliest events in infection when there are relatively few pathogens to address. The majority of vaccines are delivered systemically by the intramuscular (IM) route. While IM vaccination can drive mucosal immune responses, mucosal immunization at intranasal (IN) or oral sites can lead to better immune responses at mucosal sites of viral entry. In macaques, IN immunization with replicating single-cycle adenovirus (SC-Ads) and protein boosts generated favorable mucosal immune responses. However, there was an apparent "distance effect" in generating mucosal immune responses. IN immunization generated antibodies against HIV envelope (env) nearby in the saliva, but weaker responses in samples collected from the distant vaginal samples. To improve on this, we tested here if SC-Ads expressing genetic adjuvants could be used to amplify antibody responses in distant vaginal samples when they are codelivered with SC-Ads expressing clade C HIV env immunogen. SC-Ads env 1157 was coadministered with SC-Ads expressing 4-1BBL, granulocyte macrophage colony-stimulating factor (GMCSF), IL-21, or <i>Clostridoides difficile (C. diff.)</i> toxin fragments by IN or IM routes. These data show that vaginal antibody responses were markedly amplified after a single immunization by the IN or IM routes, with SC-Ad expressing HIV env if this vaccine is complemented with SC-Ads expressing genetic adjuvants. Furthermore, the site and combination of adjuvants appear to "tune" these antibody responses towards an IgA or IgG isotype bias. Boosting these priming SC-Ad responses with another SC-Ad or with SOSIP native-like env proteins markedly amplifies env antibody levels in vaginal washes. Together, this data may be useful in informing the choice of route of delivery adenovirus and peptide vaccines against HIV-1.