gebhart/patrepeval huggingface dataset:
Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis. (1992)

Endotoxaemia and circulating tumour necrosis factor are important prognostic factors in severe sepsis and are implicated in the pathogenesis of septic shock. Because clinical and pathological features in acute pancreatitis are similar to septic shock this study sought to determine whether endotoxin and tumour necrosis factor were prognostic factors in 38 patients with prognostically severe acute pancreatitis. Endotoxaemia, present in 19/37 (51%) patients on day 1, was more common in nonsurvivors than survivors (10/11, 91% v 9/26, 35%, p = 0.003). Day 1 serum endotoxin concentrations were higher in patients with a severe outcome (median (interquartile range) 314 (173-563) pg/ml v 0 (0-185) pg/ml, p<0.01) and in non-survivors (266 (173-586) pg/ml v 0 (0-165) pg/ml, p<0.01). Serum tumour necrosis factor was detectable in 47 of 109 samples (43%) from 38 patients (median 35 pg/ml, range 5-943 pg/ml). Day 1 serum tumour necrosis factor correlated with a worse prognostic score and a severe outcome in all patients (n = 38, r = 0.36, p = 0.027; r = 0.33, p<0.05) and with mortality in patients with gall stones (n = 23, r = 0.50, p = 0.02). Our data suggest that endotoxin and tumour necrosis factor could be prognostic factors in severe acute pancreatitis.
Hyperfiltration predicts long-term renal outcomes in humanized sickle cell mice (2019)

We previously reported that humanized sickle cell (HbSS) mice develop spontaneous nephropathy, a major cause of morbidity and mortality in sickle cell disease (SCD). Because sex-dependent protective mechanisms in SCD have been reported, we examined the course of nephropathy in male and female HbSS mice to determine contributors and/or predictors of disease severity. In male HbSS mice, glomerular filtration rate was characterized by a rapid onset of hyperfiltration and subsequent progressive decline of renal function over 20 weeks. Early tubular injury presented with increased excretion of kidney injury marker 1 (KIM-1), progressive loss of tubular brush border, and interstitial fibrosis that preceded the onset of glomerular damage, suggesting a tubuloglomerular mechanism of kidney injury in these mice. Additionally, we observed a strong association between the magnitude of hyperfiltration and the degree of long-term kidney injury in male HbSS mice. Unlike males, female HbSS mice did not demonstrate a significant loss of renal function or severe kidney damage during the time course of the study. These results suggest that magnitude of hyperfiltration predicts the onset of chronic kidney damage in male HbSS mice, whereas protective mechanisms in female HbSS mice delay the onset of SCD nephropathy.
Magnetic reversal spurts: Rain gauges for comet showers (1988)

Abrupt increases in the rate of magnetic reversals (magnetic reversal spurts) were first studied by many others. They hypothesized that spurts result from increased turbulence in the earth's core dynamo during episodes of intense bolide bombardment of the earth. Mechanisms for creating episodes of intense bombardment of the earth involve gravitational perturbation of the Oort cloud of comets, either by a hidden planet, a solar companion, or massive matter in the galactic plane. Herein, the time variation in reversal rate is analyzed using methods of statistical density estimation. A smooth, continuous estimate of reversal rate is obtained using an adaptive kernel method, in which the kernel width is adjusted as a function of reversal rate. The estimates near the ends of the data series (at 165 my ago and the present) are obtained by extending the data by reflection. The results show that the reversal spurts are not associated demonstrably with extinctions or well-dated impacts. If the spurts do record episodes of intense bombardment of the earth, then the mass extinctions do not, in general, occur at times of impacts. Furthermore, the large impact craters seen are not obviously related to the spurts, suggesting that the craters may have been caused by bolides of a different nature and with a different temporal pattern. However, the most simple explanation seems to be that the spurts do not record comet showers, either because the recording mechanism suggested by Muller and Morris is not effective or because comet showers are not triggered in the ways considered by Hut et al.
Inhibition of interleukin‐5 with a monoclonal antibody attenuates allergic inflammation (1997)

IL-5 is a prominent and perhaps an essential element in the induction of allergic inflammation in human asthma and other allergic diseases. Despite the strong biochemical and clinical correlates between lung eosinophilia and asthma, there is no clear understanding of how eosinophils exacerbate asthma. Antigen administration to sensitized animals produces eosinophilic infiltration that is very similar to that in man, and is prevented by administration of a neutralizing monoclonal antibody against IL-5. Mice in which the IL-5 gene is absent are unable to mount eosinophilic responses to antigen and do not sustain lung damage, but otherwise develop normally. The study of the biology of IL-5 has not only clarified the links between eosinophilia and airway hyperreactivity, but also strongly suggests that anti-IL-5 therapy may be an effective, safe, and novel way of treating human asthma and perhaps other eosinophilic diseases. There are many different potential approaches to the inhibition of IL-5, but the one most likely to provide "proof of principle" in "asthma in the wild" in man is a monoclonal antibody against IL-5.
Different expression of CD44, ICAM-1, and HSP60 on primary tumor and metastases of a human pancreatic carcinoma growing in scid mice. (2000)

Surface adhesion molecules play an important, but still not completely clarified, role in tumor metastasization. In this research, FACS analysis was employed to analyze surface expression of CD44H, CD44v5, CD44v6, ICAM-1 and HSP60 in human pancreatic adenocarcinoma cells growing in vitro or collected ex vivo from primary tumors and lung metastases of tumor-engrafted SCID mice. It was found that, in metastatic cells, the standard form of CD44 (CD44H) is down,-regulated, while a large fraction of cells express on membrane the splice variants v5/v6 and, in addition, ICAM-1 and HSP60. It was also apparent that two cell populations are present in lung metastases: a CD44neg population, including cells expressing CD44v5/v6, ICAM-1 and HSP60 and a population of CD44pos, CD44v5/v6neg, ICAM-1neg and HSP60neg cells. These results demonstrate that, in pancreatic adenocarcinomas, metastasization is correlated with expression of the CD44 variants v5 and v6. Moreover, this is the first report demonstrating HSP60 surface expression on metastatic cells.
Clinical effects of selective estrogen receptor modulators on vulvar and vaginal atrophy (2013)

SERMs that specifically target the pathophysiology underlying VVA may provide an alternative to vaginal or systemic estrogen therapy.
Single Mutation Induced H3N2 Hemagglutinin Antibody Neutralization: A Free Energy Perturbation Study (2008)

The single mutation effect on the binding affinity of H3N2 viral protein hemagglutinin (HA) with the monoclonical antibody fragment (Fab) is studied in this paper using the free energy perturbation (FEP) simulations. An all-atom protein model with explicit solvents is used to perform an aggregate of several microsecond FEP molecular dynamics simulations. A recent experiment shows that a single mutation in H3N2 HA, T131I, increases the antibody-antigen dissociation constant Kd by a factor of approximately 4000 (equivalent to a binding affinity decrease of approximately 5 kcal/mol), thus introducing an escape of the antibody (Ab) neutralization. Our FEP result confirms this experimental finding by estimating the HA-Ab binding affinity decrease of 5.2 +/- 0.9 kcal/mol but with a somewhat different molecular mechanism from the experimental findings. Detailed analysis reveals that this large binding affinity decrease in the T131I mutant is mainly due to the displacement of two bridge water molecules otherwise present in the wild-type HA/Ab interface. The decomposition of the binding free energy supports this observation, as the major contribution to the binding affinity is from the electrostatic interactions. In addition, we find that the loss of the binding affinity is also related to the large conformational distortion of one loop (loop 155-161) in the unbound state of the mutant. We then simulate all other possible mutations for this specific mutation site T131, and predict a few more mutations with even larger decreases in the binding affinity (i.e., better candidates for antibody neutralization), such as T131W, T131Y, and T131F. As for further validation, we have also modeled another mutation, S157L, with experimental binding affinity available (Kd increasing approximately 500 times), and found a binding affinity decrease of 4.1 +/- 1.0 kcal/mol, which is again in excellent agreement with experiment. These large scale simulations might provide new insights into the detailed physical interaction, possible future escape mutation, and antibody-antigen coevolution relationship between influenza virus and human antibodies.
In vitro endothelial wound repair. Interaction of cell migration and proliferation. (1990)

Most re-endothelialization requires both cell migration and cell proliferation. To study the association between cell migration and the initiation of DNA synthesis in an in vitro wound model, confluent cultures of porcine aortic endothelial cells grown on glass coverslips were scraped to remove half of the monolayer. Treatment with 1 ng/ml of taxol, a microtubule stabilizing drug, for 24 hours resulted in no visible change in F-actin or microtubule organization as assessed by fluorescence and immunofluorescence microscopy. There was, however, a reduction of wound re-endothelialization and an associated reduction in the proportion of cells with centrosomes redistributed toward the wound edge. No significant differences, however, were seen in the labeling indices for the first two rows of cells at the wound edge as revealed by 3H-thymidine autoradiography. Labeling of nuclei in Rows 3 to 8 and in a zone deeper within the monolayer was reduced in treated cultures. The data suggest that endothelial proliferation in cells within an area bordering a wound is dependent on both denudation, which is sufficient to promote maximal proliferation in the two rows adjacent to the wound, and cell migration, which is required for the propagation of proliferation in cells further away from the wound edge.
Immune Responses in Parasitic Diseases. Part A: General Concepts (1982)

Parasitic infections are incredibly varied and distinct in terms of interactions between hosts and pathogens as well as in complexity of life cycle, host range, vector or intermediary host requirements, forms of reproduction, and elicited response. A number of protozoan parasites are intracellular pathogens capable of surviving and multiplying within microbicidal cells such as macrophages. In contrast, nematodes generally do not multiply within the host, a trait that dramatically alters the epidemiologic, clinical, and immunologic consequences of infection. Parasites have acquired apparently effective mechanisms for escape from normal host defenses and clearance. These mechanisms may be classified as antigenic mimicry, antigenic depletion, antigenic variation, immunologic indifference, immunologic diversion, and immunologic subversion. A determination of the importance and relevance of these subterfuges to parasitic infection in humans and to therapeutic or prophylactic strategies is of the utmost urgency.
Dual Metabolic Defects Are Required to Produce Hypertriglyceridemia in Obese Subjects (2011)

Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects with similar levels of visceral adiposity. The results emphasize the clinical importance of assessing hypertriglyceridemic waist in obese subjects to identify subjects at high cardiometabolic risk.
Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2. (1993)

We have analyzed determinants of the synthesis and secretion of apolipoproteins including mRNA for apolipoproteins, in the human colon carcinoma cell line Caco-2 during differentiation in continuous culture. Significant increases in both cellular and secreted apolipoprotein A-I were observed early in the differentiation process. Increases in apolipoprotein B were limited to secreted protein and started later in the differentiation process. Levels of mRNA for apolipoproteins A-I, A-IV, B, C-III, and E increased significantly between the time cells reached confluence and 1 week postconfluence. The kinetics of mRNA accumulation were influenced by culture conditions. Nuclear extracts from postconfluent Caco-2 cells contained increased amounts of protein that bound to oligonucleotides containing the control regions of the apolipoprotein A-I and B genes. A competition experiment suggested that this protein recognized the control regions of both genes. We propose to name this protein DRIFT-1 (differentiation-related intestinal factor for transcription 1).
Spin-current interaction with a monodomain magnetic body: A model study (2000)

I examined the consequence of a spin-current-induced angular momentum deposition in a monodomain Stoner-Wohlfarth magnetic body. The magnetic dynamics of the particle are modeled using the Landau-Lifshitz-Gilbert equation with a phenomenological damping coefficient $\ensuremath{\alpha}.$ Two magnetic potential landscapes are studied in detail: One uniaxial, the other uniaxial in combination with an easy-plane potential term that could be used to model a thin-film geometry with demagnetization. Quantitative predictions are obtained for comparison with experiments.
High affinity germinal center B cells are actively selected into the plasma cell compartment (2006)

A hallmark of T cell-dependent immune responses is the progressive increase in the ability of serum antibodies to bind antigen and provide immune protection. Affinity maturation of the antibody response is thought to be connected with the preferential survival of germinal centre (GC) B cells that have acquired increased affinity for antigen via somatic hypermutation of their immunoglobulin genes. However, the mechanisms that drive affinity maturation remain obscure because of the difficulty in tracking the affinity-based selection of GC B cells and their differentiation into plasma cells. We describe a powerful new model that allows these processes to be followed as they occur in vivo. In contrast to evidence from in vitro systems, responding GC B cells do not undergo plasma cell differentiation stochastically. Rather, only GC B cells that have acquired high affinity for the immunizing antigen form plasma cells. Affinity maturation is therefore driven by a tightly controlled mechanism that ensures only antibodies with the greatest possibility of neutralizing foreign antigen are produced. Because the body can sustain only limited numbers of plasma cells, this "quality control" over plasma cell differentiation is likely critical for establishing effective humoral immunity.
Modification of a laser‐based flow cytometer for high‐resolution DNA analysis of mammalian spermatozoa (1986)

Modification of a Coulter EPICS V orthogonal laser-based flow cytometer/cell sorter allows resolution of X and Y mammalian sperm populations based on DNA content. The modification consists of beveling the sample injection tube situated in the flow chamber, adding a second fluorescence detector directly forward along the laser beam axis, and routing the collected fluorescence through an optical fiber bundle to one of the existing photomultiplier tubes. The X and Y chromosome-bearing spermatozoa from the bull, boar, and ram can be resolved using this system.
Exuberant, voiceless participation: an unintended consequence of dialogic sensibilities? (2016)

One approach to dialogic pedagogy focuses on the interplay of voices: Whose voices are expressed and attended to in classroom discourse? And how do these voices play off of one another in creating new ideas and meanings? In particular, to what extent are students empowered to express their own voices, rather than reproducing the teacher or textbook's authoritative discourse? We explore these questions using data from a linguistic ethnographic study of mother tongue Hebrew language lessons in two Israeli primary schools. The lessons are lively, with exuberant student participation, and on multiple occasions teachers encourage students to express their own ideas and to build on one another's contributions. Though students frequently announce their intentions to undertake dialogic speech acts, these declarations are usually ritualistic and hollow, as students animate the teachers' voice rather than offering independent or original perspectives. This paper discusses this phenomenon, revealing a potential conflict between the realization of student voice and other dialogic imperatives.
Biomimetic Synthesis of Gramicidin S and Analogues by Enzymatic Cyclization of Linear Precursors on Solid Support (2003)

[reaction: see text] Gramicidin S is a potent decapeptide antibiotic with high hemolytic activity but is unlikely to provoke microbial resistance. Here we demonstrate that gramicidin thioesterase (GrsB TE) correctly cyclizes immobilized linear decapeptide precursors into head-to-tail products, indicating its suitability for parallel solid-phase synthesis of gramicidin analogues from linear precursors on solid support. This chemoenzymatic method will enable the optimization of the therapeutic index of the natural product to fight microbial resistance.
Self-assembly of floating magnetic particles into ordered structures: A promising route for the fabrication of tunable photonic band gap materials (1999)

We report stable ordered arrays of millimeter-size magnetic particles floating on a liquid surface. Self-assembly into a regular two-dimensional lattice results from lateral magnetic interactions between the particles. The lattice constant may be easily tuned by the application of external magnetic field. The array symmetry is designed by using different particle shapes, magnets, and magnet position inside the particle, so that complex symmetries may be achieved. Three-dimensional ordered arrays are obtained in a stack of troughs containing floating magnets. Computer simulations of electromagnetic wave propagation in such three-dimensional structures suggest an opening of a tunable photonic band gap in the microwave range.
Response criteria in prostatic carcinoma. (1999)

Assessment of response in advanced prostate cancer is hampered by the preponderance of nonmeasurable, "bone-only" disease. Although bone scans are accurate in assessing new lesions, they are frequently unreliable in evaluating tumor regression. Alternatively, evaluation of response based on changes in prostate-specific antigen (PSA), a biochemical marker, is now routinely incorporated into clinical trials as a surrogate end point for response. However, despite general acceptance of its use as an end point in clinical trials, there is no standardized definition of PSA response. Furthermore, changes in PSA do not always correlate with regression of measurable tumor, especially in response to noncytotoxic agents. PSA changes are most defensibly used to define initial hints of a drug's potential usefulness, rather than as a validation of benefit. Improvement in quality of life has emerged as a clinically relevant endpoint, especially in the setting of hormone-refractory disease, in which therapy has yet to have an impact on survival. There is a current trend toward reporting response to therapy as reflecting changes in biochemical markers, measurable disease, bone-only disease, and quality of life separately, rather than trying to pigeon-hole "response" into traditional categories of "complete" and "partial." This independent reporting of outcome parameters provides a more accurate picture of the potential therapeutic benefit of the assessed new treatments, and allows more informed decision-making by physicians and their patients.
Lamellar Structures of Symmetric Diblock Copolymers:  Comparisons between Lattice Monte Carlo Simulations and Self-Consistent Mean-Field Calculations (2002)

We have conducted detailed comparisons of the predictions of self-consistent mean-field (SCMF) theory with results of Monte Carlo simulations for bulk lamellar structures of symmetric diblock copolymers A−B in concentrated solutions. Large differences are found among the values of the Flory−Huggins parameter extracted in different ways. Under the convolution approximation, we assess the accuracy of the SCMF theory by comparing simulated lamellar profiles with those obtained from the theory. A Flory−Huggins parameter inferred from the free energy of the system provides good overall agreement between simulated and theoretical lamellar profiles. The results of simulations for chain dimensions scale with the product εN, where ε denotes the repulsion between A and B segments, and N is the chain length.
Effects of aging, sex, and physical training on cardiovascular responses to exercise. (1992)

A lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise all contribute to the age-related decline in VO2max. Effects of age and training on VO2max, maximal cardiac output, and stroke volume cannot be fully explained by differences in body composition. In sedentary subjects, however, the sex difference in maximal cardiac output and stroke volume can be accounted for by the greater percentage of body fat in women than in men.
Alterations in T-Lymphocyte Subpopulations in Patients With Head and Neck Cancer: Correlations With Prognosis (1987)

Impaired cell-mediated immunity has been consistently demonstrated in patients with advanced head and neck squamous cancer (HNSC); however, the results of prior studies of correlations of cellular immune parameters with treatment outcome have been inconsistent, and routine assessment of immune parameters has been of limited clinical use. To determine the prognostic importance of alterations in the proportions of various T-lymphocyte subpopulations in the peripheral blood of patients with HNSC, levels of T3, T4, T6, T8, T9, T10, T11, and Leu 7 cells were quantitated by flow cytometry in 80 previously untreated patients and prospectively correlated with tumor characteristics and clinical course (median length of follow-up, 27 months). The mean helper/suppressor cell ratio (T4/T8) increased progressively with increasing tumor stage and was significantly elevated among patients with cancer as a group and in patients with advanced (stage III or IV) disease compared with 40 normal subjects. Decreased disease-free survival was significantly associated with elevated T4/T8 ratios and low percent T8 and T11 cell levels. The prognostic significance of percent T8 (cytotoxic/suppressor) cell levels persisted even after adjusting for known prognostic factors of tumor stage, T class, N class, and tumor site. These correlations provide new insight into immune alterations in HNSC that may prove useful in identifying patients with early clinical disease who have a poor prognosis.