gebhart/patrepeval huggingface dataset:
Clinical associations of serum interleukin-17 in systemic lupus erythematosus (2013)

Serum IL-17 concentration correlates poorly with SLE disease activity but is significantly elevated in patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6 alone to characterize Th17-driven disease, such as SLE. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE.
Angiogenesis and hypertension (1998)

Genetic and fetal influences appear to have significant effects in determining impaired vascular development as an early cause of essential hypertension.
Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems (1990)

This study was performed to examine the hypothesis that thalamic-projecting neurons of mesopontine cholinergic nuclei display activity patterns that are compatible with their role in inducing and maintaining activation processes in thalamocortical systems during the states of waking (W) and rapid-eye-movement (REM) sleep associated with desynchronization of the electroencephalogram (EEG). A sample of 780 neurons located in the peribrachial (PB) area of the pedunculopontine tegmental nucleus and in the laterodorsal tegmental (LDT) nucleus were recorded extracellularly in unanesthetized, chronically implanted cats. Of those neurons, 82 were antidromically invaded from medial, intralaminar, and lateral thalamic nuclei: 570 were orthodromically driven at short latencies from various thalamic sites: and 45 of the latter elements are also part of the 82 cell group, as they were activated both antidromically and synaptically from the thalamus. There were no statistically significant differences between firing rates in the PB and LDT neuronal samples. Rate analyses in 2 distinct groups of PB/LDT neurons, with fast (greater than 10 Hz) and slow (less than 2 Hz) discharge rates in W, indicated that (1) the fast-discharging cell group had higher firing rates in W and REM sleep compared to EEG-synchronized sleep (S), the differences between all states being significant (p less than 0.0005); (2) the slow-discharging cell group increased firing rates from W to S and further to REM sleep, with significant difference between W and S (p less than 0.01), as well as between W or S and REM sleep (p less than 0.0005). Interspike interval histograms of PB and LDT neurons showed that 75% of them have tonic firing patterns, with virtually no high-frequency spike bursts in any state of the wake-sleep cycle. We found 22 PB cells that discharged rhythmic spike trains with recurring periods of 0.8-1 sec. Autocorrelograms revealed that this oscillatory behavior disappeared when their firing rate increased during REM sleep. Dynamic analyses of sequential firing rates throughout the waking-sleep cycle showed that none of the full-blown states of vigilance is associated with a uniform level of spontaneous firing rate. Signs of decreased discharge frequencies of mesopontine neurons appeared toward the end of quiet W, preceding by about 10-20 sec the most precocious signs of EEG synchronization heralding the sleep onset. During transition from S to W, rates of spontaneous discharges increased 20 sec before the onset of EEG desynchronization.(ABSTRACT TRUNCATED AT 400 WORDS)
Duration of red blood cell storage and inflammatory marker generation. (2017)

Red blood cell (RBC) transfusion is a life-saving treatment for several pathologies. RBCs for transfusion are stored refrigerated in a preservative solution, which extends their shelf-life for up to 42 days. During storage, the RBCs endure abundant physicochemical changes, named RBC storage lesions, which affect the overall quality standard, the functional integrity and in vivo survival of the transfused RBCs. Some of the changes occurring in the early stages of the storage period (for approximately two weeks) are reversible but become irreversible later on as the storage is extended. In this review, we aim to decipher the duration of RBC storage and inflammatory marker generation. This phenomenon is included as one of the causes of transfusion-related immunomodulation (TRIM), an emerging concept developed to potentially elucidate numerous clinical observations that suggest that RBC transfusion is associated with increased inflammatory events or effects with clinical consequence.
Epigenetics: A New Challenge in the Post-Genomic Era of Livestock (2012)

Livestock genetics is currently navigating through a genomic era promoted by advances in DNA technologies. For instance, massive amounts of genomic information (e.g., arrays that genotype more than 500K SNPs along the bovine genome) are incorporated into the prediction of genetic merit providing higher predictive accuracy (Van Raden et al., 2008). This increment has led to important changes in the animal breeding industry (Dekkers, 2004; Ibanez-Escriche and Gonzalez-Recio, 2011). New advances continue, and efforts are currently placed in whole genome sequencing (e.g., in species such as cattle and swine) for its implementation future implementation to improve accuracy of genomic selection or mapping new QTL of interest (Meuwissen and Goddard, 2010).
Materials/manufacturing element of the Advanced Turbine Systems Program (1995)

The technology based portion of the Advanced Turbine Systems Program (ATS) contains several subelements which address generic technology issues for land-based gas-turbine systems. One subelement is the Materials/ Manufacturing Technology Program which is coordinated by DOE Oak Ridge Operations and Oak Ridge National Laboratory (ORNL). The work in this subelement is being performed predominantly by industry with assistance from universities and the national laboratories. Projects in this sub-element are aimed toward hastening the incorporation of new materials and components in gas turbines.
Identification of a Gene Expression Signature Associated with Recurrent Disease in Squamous Cell Carcinoma of the Head and Neck (2004)

Molecular studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated multiple genetic abnormalities such as activation of various oncogenes (Ras, Myc, epidermal growth factor receptor, and cyclin D1), tumor suppressor gene inactivation (TP53 and p16), and loss of heterozygosity at numerous chromosomal locations. Despite these observations, accurate and reliable biomarkers that predict patients at highest risk for local recurrence have yet to be defined. In an effort to identify gene expression signatures that may serve as biomarkers, we studied 41 squamous cell carcinoma tumors (25 primary and 16 locally recurrent) from various anatomical sites and 13 normal oral mucosal biopsy samples from healthy volunteers with microarray analysis using Affymetrix U133A GeneChip arrays. Differentially expressed genes were identified by calculating generalized t tests (P < 0.001) and applying a series of filtering criteria to yield a highly discriminant list of 2890 genes. Hierarchical clustering and image generation using standard software were used to visualize gene expression signatures. Several gene expression signatures were readily identifiable in the HNSCC tumors, including signatures associated with proliferation, extracellular matrix production, cytokine/chemokine expression, and immune response. Of particular interest was the association of a gene expression signature enriched for genes involved in tumor invasion and metastasis with patients experiencing locally recurrent disease. Notably, these tumors also demonstrated a marked absence of an immune response signature suggesting that modulation of tumor-specific immune responses may play a role in local treatment failure. These data provide evidence for a new gene expression-based biomarker of local treatment failure in HNSCC.
Transmission Electron Microscopy of Shape-Controlled Nanocrystals and Their Assemblies (2000)

The physical and chemical properties of nanophase materials rely on their crystal and surface structures. Transmission electron microscopy (TEM) is a powerful and unique technique for structure characterization. The most important application of TEM is the atomic-resolution real-space imaging of nanoparticles. This article introduces the fundamentals of TEM and its applications in structural determination of shape-controlled nanocrystals and their assemblies. By forming a nanometer size electron probe, TEM is unique in identifying and quantifying the chemical and electronic structure of individual nanocrystals. Electron energy-loss spectroscopy analysis of the solid-state effects and mapping the valence states are even more attractive. In situ TEM is demonstrated for characterizing and measuring the thermodynamic, electric, and mechanical properties of individual nanostructures, from which the structure−property relationship can be registered with a specific nanoparticle/structure.
Mitochondrial Susceptibility to Oxidative Stress Exacerbates Cerebral Infarction That Follows Permanent Focal Cerebral Ischemia in Mutant Mice with Manganese Superoxide Dismutase Deficiency (1998)

Mitochondrial injury has been implicated in ischemic neuronal injury. Mitochondria, producing adenosine triphosphate by virtue of electron flow, have been shown to be both the sites of superoxide anion (O2-) production and the target of free radical attacks. We evaluated these mechanisms in an in vivo cerebral ischemia model, using mutant mice with a heterozygous knock-out gene (Sod2 -/+) encoding mitochondrial manganese superoxide dismutase (Mn-SOD). Sod2 -/+ mice demonstrated a prominent increase in O2- production under normal physiological conditions and in ischemia, as evidenced by specific oxidation of a fluorescent probe, hydroethidine, reflecting decreased activity of Mn-SOD. A mitochondrial viability assay that used rhodamine 123, which is accumulated by transmembrane potential of viable mitochondria, demonstrated accelerated development of mitochondrial injury. This rapid progress of ischemic injury resulted in exacerbation of infarct size and hemisphere enlargement, causing advanced neurological deficits but without altering DNA fragmentation induction. The present study suggests that O2- overproduced in a mitochondrial compartment, when uncoupled from antioxidant defenses, induces impairment of mitochondrial function and causes exacerbation of cerebral infarction after ischemia.
A technique for measurement of the extent of spatial organization of atrial activation during atrial fibrillation in the intact human heart (1995)

Atrial fibrillation (AF) is a common clinical problem, associated with considerable morbidity and mortality, for which effective management strategies have yet to be devised. The absence of objective measures to guide selection of antiarrhythmic drug therapy for maintenance of sinus rhythm leaves only clinical endpoints (either beneficial or detrimental) for assessment of drug action, with occasional catastrophic consequences. As part of an attempt to provide an objective framework for the assessment of antiarrhythmic drug action on the electrophysiologic determinants of atrial fibrillation, we have developed a measure of the spatial organization of atrial activation processes during atrial fibrillation. By recording activation sequences at multiple equally spaced locations on the endocardial surface of the atria during atrial fibrillation in humans and determining the degree of correlation between these activation sequences as a function of distance, we have been able to construct spatial correlation functions for atrial activation. We have found that atrial activation remains well-correlated, independent of distance during normal sinus rhythm and atrial flutter. During atrial fibrillation, correlation decays monotonically with distance and the space-constant for this decay may be used to describe the relative spatial organization of atrial fibrillation. We provide examples of the impact of antiarrhythmic agents on the space-constant and suggest that assessment of the relative spatial organization of atrial activation using this methodology may potentially provide an objective framework to guide therapy in patients with AF.
Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-γ-lyase function (2015)

Glioblastoma multiforme (GBM) is one of the most common encephalic malignant tumors. Due to a high recurrence rate and a lack of effective treatments, the average survival rate remains low. Temozolomide (TMZ), a class of alkylating agent, is widely used as a first-line therapeutic drug during the adjuvant treatment for GBM patients. However, most patients exhibit a palpable resistance to TMZ treatment. Additionally, the underlying mechanism remains to be clarified. In this study, glutathione (GSH) and reactive oxygen species (ROS) levels were found to be closely associated with the sensitivity of GBM cells to TMZ. We also found that TMZ markedly induced xCT, the subunit of glutamate/cystine transporter system xc- expression, which together with the GSH synthesis was increased while the TMZ-inducible ROS level was decreased in GBM cells. In addition, the cystathionine γ-lyase (CTH) acivity, a key enzyme in the transsulfuration pathway was enhanced by TMZ, which insured a cysteine supply and GSH synthesis in a compensatory manner when xCT was blocked. Thus, the individual inhibition of xCT by siRNA and a pharmacological inhibitor (sulfasalazine) only partially inhibited GSH synthesis and moderately enhanced the GBM cell sensitivity to TMZ. However, the TMZ‑induced cytotoxicity was markedly increased along with a marked decrease in GSH levels as result of co-treatment with erastin, which inhibited cysteine uptake from xCT transporter and suppressed CTH activity, leading to impaired transformation from methionine to cysteine. In conclusion, to GBM therapy with a drug combination of TMZ and erastin may be beneficial.
Blocking Thrombospondin-1/CD47 Signaling Alleviates Deleterious Effects of Aging on Tissue Responses to Ischemia (2007)

With increasing age and diet-induced atherosclerotic vascular disease, TSP1 and its receptor CD47 become more limiting for blood flow and tissue survival after ischemic injury. Drugs that limit TSP1/CD47 regulation of blood flow could improve outcomes from surgical interventions in the elderly and ameliorate vascular complications attendant to aging.
Serum and Urinary Cell–free MiR-146a and MiR-155 in Patients with Systemic Lupus Erythematosus (2010)

The results suggested that serum miR-146a and miR-155 participate in the pathophysiology of SLE and might be used as biomarkers of SLE.
VEGF antagonists (2001)

The majority of cancer have an absolute requirement for angiogenesis, the process by which new blood vessels are formed. The most potent angiogenic cytokine is vascular endothelial growth factor (VEGF) and there has been substantial research into the development of VEGF/VEGF receptor (VEGFR) antagonists. To date these strategies have included gene therapy techniques that deliver antisense oligonucleotides, soluble VEGFRs that function in a dominant negative fashion and ribozymes. Additional strategies have included the development of receptor tyrosine kinase (RTK) inhibitors and monoclonal antibodies (mAbs) directed against VEGF or the signalling receptor. The most promising agents appear to be the monoclonal anti-VEGF antibodies and the RTK inhibitors as these have demonstrated broad spectrum antitumour activity in vivo and single agent activity in early phase clinical trials in patients with advanced pre-treated breast and colorectal carcinoma and Kaposi's sarcoma. The RTK inhibitors are of particular interest as they can be administered by mouth. Collation of the early clinical trial data suggests that VEGF antagonists are largely well-tolerated but may be associated with vascular toxicities such as haemorrhage and thromboembolic events. Combination studies of chemotherapy and VEGF antagonists are underway but the benefit of these regimens will need to be established in adequately powered Phase III studies. Potentially these agents may play a role in the treatment of both early (adjuvant) and advanced cancer. The efficacy of the drugs will be explored in a number of non-malignant conditions including rheumatoid arthritis (RA), psoriasis, diabetic retinopathy and possibly as non-steroidal contraceptives but the overall clinical development of these agents can only be optimised if appropriate biological end points are identified and incorporated into clinical trials.
Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation (1992)

Treatment of T cells with the cysteine protease bromelain has been widely used to enhance the binding of human T cells to human E (autologous E rosettes) and has been shown to remove surface T cell CD44 molecules. Ligand binding to CD44 has been shown to markedly augment T cell activation. To study the activation potential of bromelain-treated CD44 T cells, we have compared the proliferation of sham- and bromelain-treated normal human PBMC to mitogenic CD2 mAb. We found that bromelain not only removed T cell CD44, but also removed the CD45RA isoform of CD45 as well as E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 molecules. T cell proliferation in response to CD2 mAb was increased 325% in bromelain-treated PBMC compared to sham-treated PBMC (p < 0.005). Reciprocal treatment experiments using purified T cells and monocytes demonstrated that the enhancement of T cell CD2 activation by bromelain occurred only when T cells were treated with bromelain and was accompanied by increased adhesion of T cells to monocytes. These data demonstrate that expression of portions of the extracellular domains of the CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules are not required for CD2 activation of human T cells. Rather, the removal of these surface molecules by bromelain is associated with enhanced T cell-monocyte aggregation and enhanced CD2-mediated T cell activation. Taken together with data that CD44, E2/MIC2, CD6, and CD7 mAb inhibit CD2/lymphocyte function-associated Ag-3-mediated cellular interactions and also augment CD2-mediated triggering of T cells, these data suggest that members of the bromelain-sensitive group of surface molecules may comprise a set of CD2-associated adhesion ligands that acts in concert to modulate human T cell activation.
Legal Aspects Of The Economic Relationship Between Physicians And Hospitals (1984)

Journal For Healthcare Quality: October 1, 1984 - Volume 6 - Issue 4 - p 5-8 doi: 10.1111/j.1945-1474.1984.tb00694.x
Low-level predation by lytic phage phiIPLA-RODI promotes biofilm formation and triggers the stringent response in Staphylococcus aureus (2017)

An important lesson from the war on pathogenic bacteria has been the need to understand the physiological responses and evolution of natural microbial communities. Bacterial populations in the environment are generally forming biofilms subject to some level of phage predation. These multicellular communities are notoriously resistant to antimicrobials and, consequently, very difficult to eradicate. This has sparked the search for new therapeutic alternatives, including phage therapy. This study demonstrates that S. aureus biofilms formed in the presence of a non-lethal dose of phage phiIPLA-RODI exhibit a unique physiological state that could potentially benefit both the host and the predator. Thus, biofilms formed under phage pressure are thicker and have a greater DNA content. Also, the virus-infected biofilm displayed major transcriptional differences compared to an untreated control. Significantly, RNA-seq data revealed activation of the stringent response, which could slow down the advance of the bacteriophage within the biofilm. The end result would be an equilibrium that would help bacterial cells to withstand environmental challenges, while maintaining a reservoir of sensitive bacterial cells available to the phage upon reactivation of the dormant carrier population.
Mathematical modeling of drop mixing in a slit-type microchannel (2001)

Fast solute mixing can be achieved in a microchannel by rapid unidirectional displacement of a discrete liquid drop. The recirculation streamlines created within the liquid during the drop's motion cause the solute to interlayer across the channel depth, provided the interlayer diffusion of the solute is small. Uniform interlayering appears when the drop is displaced by more than three drop lengths in a slit-type microchannel, thereby reducing the solute diffusion distances to a fraction of the channel depth. By fabricating the microchannel to a depth of less than 50 m even large molecules with a low diffusivity (D < 10 -8 cm 2 s -1 ) can be mixed in seconds. The above strategy is shown by modeling the mixing of solutes present in a drop moving in a slit-type microchannel.
Isolation and Characterization of a Gene Affecting Fatty Acid Elongation in Saccharomyces cerevisiae (1996)

Fatty acid elongation defective mutants were isolated from Saccharomyces cerevisiae by mutagenizing strains that were defective in fatty acid synthase (FAS) activity. Cells of the fatty acid synthase-defective strains can grow when supplemented with tetradecanoic acid (14:0) due to the presence of membrane bound elongation systems that can extend the 14 carbon fatty acid to longer chain species. After mutagenesis and rescue on medium containing a mixture of 14:0, 16:0 and 18:0, cells were screened for their inability to grow on medium containing only 14:0. From 150,000 colonies, four stable isolates were identified, all of which appear to represent the same complementation group. Gas chromatography of lipid extracts from mutant elo1-1 (designated as elongation defective) cells grown with long or medium chain fatty acids indicates that it fails to efficiently elongate (12, 13, or 14) carbon fatty acids. A gene disrupted fas2Delta::LEU2;elo1Delta::HIS3 mutant incorporates 14-18-carbon fatty acids into membrane lipids, indicating that fatty acid transport is not affected by the mutation. Molecular cloning and sequence analysis of the ELO1 gene suggests that the encoded protein is a membrane bound polypeptide that contains at least five potential membrane spanning regions and a presumptive NADPH binding site. Analysis of the ELO1 mRNA levels indicates that the gene is expressed in cells grown on fatty acid deficient medium. It is rapidly induced in wild type cells that are supplemented with 14:0 and is repressed when cells are supplied with 16- and 18-carbon fatty acids.
Platform for Induction and Maintenance of Transgene-free hiPSCs Resembling Ground State Pluripotent Stem Cells (2014)

Cell banking, disease modeling, and cell therapy applications have placed increasing demands on hiPSC technology. Specifically, the high-throughput derivation of footprint-free hiPSCs and their expansion in systems that allow scaled production remains technically challenging. Here, we describe a platform for the rapid, parallel generation, selection, and expansion of hiPSCs using small molecule pathway inhibitors in stage-specific media compositions. The platform supported efficient and expedited episomal reprogramming using just OCT4/SOX2/SV40LT combination (0.5%-4.0%, between days 12 and 16) in a completely feeder-free environment. The resulting hiPSCs are transgene-free, readily cultured, and expanded as single cells while maintaining a homogeneous and genomically stable pluripotent population. hiPSCs generated or maintained in the media compositions described exhibit properties associated with the ground state of pluripotency. The simplicity and robustness of the system allow for the high-throughput generation and rapid expansion of a uniform hiPSC product that is applicable to industrial and clinical-grade use.