gebhart/patrepeval huggingface dataset:
Ageing, tumour necrosis factor-alpha (TNF-α) and atherosclerosis (2000)

SUMMARY Ageing is associated with increased inflammatory activity in the blood. The purpose of this study was to investigate if age-related increased plasma levels of TNF-α were associated with atherosclerosis in a cohort of 130 humans aged 81 years. The elderly cohort had increased circulating levels of TNF-α, C-reactive protein (CRP), total cholesterol (TC), low-density lipoproteins (LDL) and a low high-density lipoprotein (HDL)/TC ratio compared with a young control group (n = 44). The elderly cohort was divided by tertiles into three subgroups with low, intermediate, and high levels of TNF-α, respectively. In the group with high TNF-α concentrations a significantly larger proportion had clinical diagnoses of atherosclerosis. Furthermore, weak correlations were found between TNF-α on one hand and blood concentrations of triglycerides, leucocytes, CRP and a low HDL/TC ratio on the other which are known as risk factors of atherogenesis and thromboembolic complications. No correlations were found between TNF-α, TC, LDL, or the body mass index. In conclusion, the present study shows that in a cohort of 81-year-old humans, high levels of TNF-α in the blood were associated with a high prevalence of atherosclerosis.
Protein Minimization of the gp120 Binding Region of Human CD4 (2005)

CD4 is an important component of the immune system and is also the cellular receptor for HIV-1. CD4 consists of a cytoplasmic tail, one transmembrane region, and four extracellular domains, D1-D4. Constructs consisting of all four extracellular domains of human CD4 as well as the first two domains (CD4D12) have previously been expressed and characterized. All of the gp120-binding residues are located within the first N-terminal domain (D1) of CD4. To date, it has not been possible to obtain domain D1 alone in a soluble and active form. Most residues in CD4 that interact with gp120 lie within the region 21-64 of domain D1 of CD4. On the basis of these observations and analysis of the crystal structure of CD4D12, a mutational strategy was designed to express CD4D1 and region 21-64 of CD4 (CD4PEP1) in Escherichia coli. K(D) values for the binding of CD4 analogues described above to gp120 were measured using a Biacore-based solution-phase competition binding assay. Measured K(D) values were 15 nM, 40 nM, and 26 microM for CD4D12, CD4D1, and CD4PEP1, respectively. All of the proteins interact with gp120 and are able to expose the 17b-binding epitope of gp120. Structural content was determined using CD and proteolysis. Both CD4D1 and CD4PEP1 were partially structured and showed an enhanced structure in the presence of the osmolyte sarcosine. The aggregation behavior of all of the proteins was characterized. While CD4D1 and CD4PEP1 did not aggregate, CD4D12 formed amyloid fibrils at neutral pH within a week at 278 K. These CD4 derivatives should be useful tools in HIV vaccine design and entry inhibition studies.
Regulatory role of B-1 B cells in chronic colitis (2008)

According to the 'hygiene hypothesis', enhanced microbial exposure due to early childhood infections leads to a reduction of T(h)2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of T(h)2-mediated colitis of the TCRalpha knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCRalpha KO mice kept in the CV facility developed dramatically less colitis than mice that were kept in the SPF facility. Surprisingly, the suppression of colitis in the CV facility correlated with a significant increase in natural IgM production by B-1 B cells. In contrast, B cell-deficient TCRalpha double-knockout (alphamu DKO) mice maintained in the CV facility continued to develop severe colitis, strongly suggesting that B-1 B cells contributed to the suppression of colitis. Indeed, the adoptive transfer of B-1 B cells isolated from the peritoneal cavity of TCRalpha KO mice (SPF) into alphamu DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in T(h)2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora.
Single-Dose Mucosal Immunization with Biodegradable Microparticles Containing aSchistosoma mansoniAntigen (1999)

ABSTRACT The purpose of this work was to assess the immunogenicity of a single nasal or oral administration of recombinant 28-kDa glutathione S -transferase of Schistosoma mansoni (rSm28GST) entrapped by poly(lactide-co-glycolide) (PLG)- or polycaprolactone (PCL)-biodegradable microparticles. Whatever the polymer and the route of administration used, the equivalent of 100 μg of entrapped rSm28GST induced a long-lasting and stable antigen-specific serum antibody response, with a peak at 9 to 10 weeks following immunization. Isotype profiles were comparable, with immunoglobulin G1 being the predominant isotype produced. The abilities of specific antisera to neutralize the rSm28GST enzymatic activity have been used as criteria of immune response quality. Pooled 10-week sera from mice receiving PLG microparticles by the nasal or oral route neutralized the rSm28GST enzymatic activity, whereas sera of mice receiving either PCL microparticles, free rSm28GST, or empty microparticles inefficiently neutralized this enzymatic activity. Finally, this study shows that a single administration of these microparticles could provide distinct and timely release pulses of microencapsulated antigen, which might greatly facilitate future vaccine development.
PPARα ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity (2004)

Previous studies demonstrated that during cisplatin-induced acute renal failure, there is a significant reduction in proximal tubule fatty acid oxidation. We now report on the effects of peroxisome proliferator-activated receptor-alpha (PPAR alpha) ligand Wy-14643 (WY) on the abnormalities of medium chain fatty acid oxidation and pyruvate dehydrogenase complex (PDC) activity in kidney tissue of cisplatin-treated mice. Cisplatin causes a significant reduction in mRNA levels and enzyme activity of mitochondrial medium chain acyl-CoA dehydrogenase (MCAD). PPAR alpha ligand WY ameliorated cisplatin-induced acute renal failure and prevented cisplatin-induced reduction of mRNA levels and enzyme activity of MCAD. In contrast, in cisplatin-treated PPAR alpha null mice, WY did not protect kidney function and did not reverse cisplatin-induced decreased expression of MCAD. Cisplatin inhibited renal PDC activity before the development of acute tubular necrosis, and PDC inhibition was reversed by pretreatment with PPAR alpha agonist WY. Cisplatin also induced increased mRNA and protein levels of pyruvate dehydrogenase kinase-4 (PDK4), and PPAR alpha ligand WY prevented cisplatin-induced increased expression of PDK4 protein levels in wild-type mice. We conclude that PPAR alpha agonists have therapeutic potential for cisplatin-induced acute renal failure. Use of PPAR alpha ligands prevents acute tubular necrosis by ameliorating cisplatin-induced inhibition of two distinct metabolic processes, MCAD-mediated fatty acid oxidation and PDC activity.
The twin questions of personalized medicine: who are you and whom do you most resemble? (2009)

Personalized medicine is typically described as the use of molecular or genetic characteristics to customize therapy. This perspective at best provides an incomplete model of the patient and at worst can lead to grossly inappropriate practices. Personalization of medicine requires two characterizations: a well-grounded understanding of who the patient is and an equally robust understanding of the subpopulation that most resembles that patient in the context of the decisions at hand. These characterizations are readily represented probabilistically and can be used to drive decision-making in a rational manner that maximizes the positive outcomes for the patient.
Identification of homing receptors that mediate the recruitment of CD4 T cells to the genital tract following intravaginal infection with Chlamydia trachomatis (1997)

Murine genital infection induced with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn) elicits a short-lived protective immunity mediated primarily by Th1 CD4 cells. To understand the development of local cell-mediated immunity against C. trachomatis infection, we investigated the mechanism(s) which mediates CD4 lymphocyte migration to the genital mucosa by identifying molecules that could support this process. We found that primarily CD4 cells were recruited to the genital tract (GT) during primary and challenge MoPn infection. Peak levels were found 21 days after primary inoculation (15.4% +/- 2.7%) and 7 days (31.3% +/- 8.5%) after challenge but diminished after resolution of infection. The CD4 cells appeared to be recruited to the GT in response to infection since these cells expressed the profile of activated, or memory, cells. We also observed up-regulation of homing receptors containing LFA-1 (CD11a) and alpha4 (CD49d) on GT CD4 cells over the course of infection. Furthermore, the mucosal homing receptor chain, beta7, but not the peripheral homing receptor chain beta1 (CD29), was detected on GT CD4 cells. MoPn-infected GT tissue expressed the endothelial cell ligands vascular cell adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), which correspond to the homing receptors on GT CD4 cells. Interestingly, VCAM-1 and MAdCAM-1 were not expressed in the GTs of uninfected mice but were temporarily induced following infection, indicating that expression of endothelial ligands in the GT are regulated by chlamydial infection. These data suggest that recruitment of CD4 cells to the GT is mediated through LFA-1:ICAM-1 and alpha4beta7:MAdCAM-1-VCAM-1 interactions.
Neuroprotection from Complement‐Mediated Inflammatory Damage (2004)

Several neurodegenerative disorders, such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are associated with inflammatory damage. The complex process of neuroinflammation involves various components of the immune system and the central nervous system. Particularly, brain astrocytes and microglial cells generate several inflammatory mediators like cytokines, leukotrienes, superoxide radicals, eicasonoids, and the components of the complement cascade. Complement plays an important role in the etiology of most of the neuroinflammatory disorders. To prevent long-term dysfunction inflammation in the central nervous system must be modulated with neuroprotective agents such as nonsteroidal anti-inflammatory drugs, steroids, phenolic thiazoles, nitrones, catechins, nitric oxide synthetase inhibitors, flavonoids, and phosphodiesterase inhibitors. Few drugs are found to be effective and their therapeutic benefit is hampered by side effects. Most of the neuroprotective agents are free radical scavengers and many inhibit only one or two aspects of inflammation. The complement inhibitory activity of most of these agents is either unknown or not established. Thus, there is doubt regarding their therapeutic value in most of the inflammatory disorders in which complement plays a major role. In this context the role of a multifunctional protein, vaccinia virus complement control protein (VCP), is quite significant as it may play a pivotal role in the treatment of several neuroinflammatory disorders. VCP is known to inhibit both complement pathways involved in inflammation. It is also known to inhibit cytokines and chemokines in inflammation. Our recent studies on rats demonstrate that VCP administration inhibits macrophage infiltration, reduces spinal cord destruction, and improves motor skills associated with spinal cord injury, establishing VCP as a strong candidate for neuroprotection. Thus, complement inhibitors such as VCP can serve as neuroprotective agents in inflammation associated with several neurodegenerative disorders.
Deep Supervised, but Not Unsupervised, Models May Explain IT Cortical Representation (2014)

Inferior temporal (IT) cortex in human and nonhuman primates serves visual object recognition. Computational object-vision models, although continually improving, do not yet reach human performance. It is unclear to what extent the internal representations of computational models can explain the IT representation. Here we investigate a wide range of computational model representations (37 in total), testing their categorization performance and their ability to account for the IT representational geometry. The models include well-known neuroscientific object-recognition models (e.g. HMAX, VisNet) along with several models from computer vision (e.g. SIFT, GIST, self-similarity features, and a deep convolutional neural network). We compared the representational dissimilarity matrices (RDMs) of the model representations with the RDMs obtained from human IT (measured with fMRI) and monkey IT (measured with cell recording) for the same set of stimuli (not used in training the models). Better performing models were more similar to IT in that they showed greater clustering of representational patterns by category. In addition, better performing models also more strongly resembled IT in terms of their within-category representational dissimilarities. Representational geometries were significantly correlated between IT and many of the models. However, the categorical clustering observed in IT was largely unexplained by the unsupervised models. The deep convolutional network, which was trained by supervision with over a million category-labeled images, reached the highest categorization performance and also best explained IT, although it did not fully explain the IT data. Combining the features of this model with appropriate weights and adding linear combinations that maximize the margin between animate and inanimate objects and between faces and other objects yielded a representation that fully explained our IT data. Overall, our results suggest that explaining IT requires computational features trained through supervised learning to emphasize the behaviorally important categorical divisions prominently reflected in IT.
Análisis de las situaciones de vulnerabilidad de la primera infancia en caldas: una mirada desde las voces de niños, niñas, padres y agentes institucionales (2011)

En el marco de la Maestría en Educación desde la Diversidad, y a partir del proceso llevado a cabo con el Plan Estratégico Departamental de Primera Infancia PI para Caldas, se realizó esta investigación que pretende generar conocimiento en torno a la percepción sobre los factores de vulnerabilidad de la infancia.Desde la perspectiva de estudio se exploran las condiciones contextuales que rodean el desarrollo infantil, la situación de las familias y la realidad de las políticas dirigidas a la niñez desde el diálogo entre la tradición académica y las voces de los actores sociales, el conocimiento científico y el social, para dilucidar sus condiciones objetivas de vida.De acuerdo con los objetivos de la investigación, la reflexión teórica parte de la concepción del desarrollo humano como el proceso mediante el cual se generan cambios que propenden por la cualificación y la construcción permanente del sujeto en interacción con el mundo simbólico, material y social.Se desarrolló igualmente una reflexión conceptual sobre la noción de vulnerabilidad y PI, como referentes iluminadores. El diseño de la investigación fue de carácter cualitativo, con enfoque interpretativo para lograr una aproximación a la realidad compleja argumentando sus matices, entrecruzamientos, contradicciones y similitudes, que permitiera dilucidar diferentes formas de expresión de la PI, a partir de las percepciones de niños - niñas, padres – cuidadores y agentes institucionales.Metodológicamente se desarrollaron tres momentos: el primero describió las concepciones sobre niñez y políticas, y las situaciones y condiciones de vulnerabilidad desde las voces de los actores participantes. En el segundo momento, se desarrolló una aproximación interpretativa para identificar tendencias y categorías emergentes, y en el tercero, una tematización desde la triangulación de la información derivada de los instrumentos, en diálogo también con la teoría y las posturas de las investigadoras.Las tendencias halladas develan tensiones y categorías emergentes relacionadas con las dimensiones materiales, institucionales, dimensión simbólica y política. Estas dimensiones permiten profundizar la comprensión sobre las relaciones inter-humanas relacionadas con el desarrollo de niños y niñas, el cumplimiento de los derechos, las relaciones y creaciones simbólicas, las relaciones con el contexto y las condiciones sociales de vida.
Translational Toxicology and the Work of the Predictive Safety Testing Consortium (2009)

Toxicology has always been translational—at least with respect to its primary focus on human “health.” The earliest “toxicologists” explored the effects of plant and animal poisons on humans, conducting experiments on (often unsuspecting) human subjects.1 Not until the sulfanilamide disaster of 1937, the 1938 US Federal Food, Drug and Cosmetic Act, and the Nuremberg Code did animals become central to the experimental assessment of chemical safety.2,3 Now, with harmonization of requirements among various international regulatory agencies, the types and design of safety evaluation studies conducted to support first-in-human investigations have been reasonably standardized.4 Most drug safety studies are conducted in both a rodent and a nonrodent species, with the aim of identifying adverse reactions relevant to human health, potential target organs of toxicity, a dose for first-in-human studies, a margin of safety between the efficacious and toxic doses, and strategies for monitoring safety during clinical trials.5 Clinical Pharmacology & Therapeutics (2009); 85, 3, 327–330 doi:10.1038/clpt.2008.270
Development of simple coupling-capacitor voltage transformer for GIS (2002)

A magnetic voltage transformer (VT), with a secondary load of more than 50 VA, is usually used for a GIS. However, the capacity of the load is too large and not economical since the load of A/D converter of a digitized control switchboard (DCS) is recently limited to only several VA. Therefore, the authors have developed a simple voltage transformer (SVT) of coupling-capacitor type to meet the performances of DCS with low load, by inserting a cylindrical capacitor electrode into the branch bus of a GIS. To maintain the required accuracy of /spl plusmn/3%, the secondary output voltages from the SVT were corrected by the numerical control process unit of the DCS in this system, since the voltages were influenced by variation in external load. Coaxial cables were also applied as a measure against temperature variation. As a result, they found that the developed SVT provided accuracy of within /spl plusmn/3% in ambient temperature between -20/spl deg/C to +60/spl deg/C.
Costimulatory approaches to adoptive immunotherapy (1998)

Costimulation is critical for induction of full T-cell effector function, and thus represents an attractive immunotherapeutic approach for the treatment of cancer. This review examines these approaches, including ex vivo T-cell expansion, systemic "delivery" of constimulation, tumors transduced or transfected with costimulatory ligands, and vaccine strategies using coimmunization with the genes for costimulatory ligands. Impressive results in animal models have been demonstrated and a wide range of human clinical trials are underway.
Enhanced adhesion with pedestal-shaped elastomeric stamps for transfer printing (2012)

Microscale elastomeric relief structures with “pedestal” shapes provide enhanced operation in stamps designed for deterministic materials assembly via transfer printing. Experimental measurements of adhesion and finite element analysis both show that for certain geometries, exceptionally large enhancements in adhesion strength (over 15×) can be achieved. Transfer printing of microscale platelets of silicon and ultrathin gallium nitride light emitting diodes onto a silicon substrate without adhesive coatings demonstrates some capabilities in assembly that result from this type of stamp, of interest in diverse applications, including those that involve heterogeneous materials integration.
Pharmacokinetics and Safety of Epinephrine Use in Liposuction (2004)

Patients are routinely exposed to high-dose epinephrine infiltration during large-volume liposuction. Because of the serious cardiovascular side-effect profile of catecholamine overdose, the authors examined the safety of larger-volume liposuction by assessing epinephrine pharmacokinetics. Five female volunteers with American Society of Anesthesiologists physical status of I or II, aged 29 to 40 years and weighing 75.9 to 95 kg, underwent liposuction. The wetting solution contained 7.3 mg (SEM, 0.7 mg) of epinephrine, corresponding to 0.09 mg/kg (0.04 mg/kg). Total plasma epinephrine and norepinephrine concentrations were assessed by high-performance liquid chromatography. Approximate exogenous epinephrine absorption was calculated after correction for estimated endogenous epinephrine production. Pharmacokinetic assessments were performed using standard equations. The total plasma epinephrine peak occurred at the final intraoperative reading (5 hours after induction) and was 323 pg/ml (24.8 pg/ml), three to four times maximum baseline resting levels. The norepinephrine level was slightly elevated throughout the study period, with a reversal of the normal epinephrine/norepinephrine ratio (<0.5:1) demonstrated intraoperatively (>5:1). Estimated time to peak exogenous epinephrine level ranged from 1 to 4 hours from the start of infiltration. Area under the plasma concentration versus time curve was approximately 2089 to 2610 pg x hour/ml. Peak exogenous epinephrine concentration was estimated to be 286 to 335 pg/ml. Clearance was 764,508 ml/hour and volume of distribution was 0.4 liter/kg (0.006 liter/kg). Total absorbed epinephrine was estimated, 1.8 mg to 2.2 mg, equivalent to 25 to 32 percent of the infiltrated dose. The reversal of the normal epinephrine/norepinephrine ratio and the fact that norepinephrine levels were within normal range implied that the majority of plasma epinephrine measured was exogenously infiltrated and not endogenously synthesized. On the basis of these observations, pharmacokinetic analyses were performed. Although unequivocal toxic epinephrine levels were not demonstrated, epinephrine peaks were three to four times the maximum observed in normal resting patients. Peak levels were comparable to those observed during major physiologic stresses, such as exercising to exhaustion, open abdominal surgery, or cross-clamping the aorta during surgical repair. Furthermore, epinephrine has been associated with myocardial infarction, arrhythmias, and fatal asystole in susceptible patients at these levels. Patients should be carefully screened for clinical evidence of hemodynamic and cardiac pathology before larger-volume liposuction is undertaken, as it may result in unnecessary high risk for patients who have preexisting cardiovascular disorders. Healthy American Society of Anesthesiologists physical status I or II patients should have sufficient cardiac reserve to tolerate these catecholamine levels.