gebhart/patrepeval huggingface dataset:
Characterization of Two Adhesins of Bordetella pertussis for Human Ciliated Respiratory-Epithelial Cells (1985)

Bordetella pertussis, the causative agent of whooping cough, adheres specifically to human ciliated respiratory-epithelial cells. In order to identify the adhesins of Bordetella, we tested mutant strains, each deficient in one of several bacterial virulence factors, for the ability to adhere to single, human ciliated cells in vitro. Loss of adherence was associated with lack of secretion of either of two surface antigens: filamentous hemagglutinin or pertussis toxin. These strains regained adherence if both components were present in the assay system (i.e., the missing protein was supplied exogenously). In this instance, both bacterial components were found bound to the surface of all the Bordetella strains tested as well as to cilia. We hypothesize that filamentous hemagglutinin and pertussis toxin, two naturally secreted surface antigens, act in concert as adhesins of Bordetella for human cilia.
Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function (2012)

BTS for pain relief in patients with chronic pancreatitis reduced adrenomedullary function, due to disruption of the efferent sympathetic fibers to the adrenal gland. BTS did not affect noradrenergic sympathetic activity, although blood pressure was lower after the sympathectomy.
Invited Review: Mechanisms of ventilator-induced lung injury: a perspective (2000)

Despite advances in critical care, the mortality rate in patients with acute lung injury remains high. Furthermore, most patients who die do so from multisystem organ failure. It has been postulated that ventilator-induced lung injury plays a key role in determining the negative clinical outcome of patients exposed to mechanical ventilation. How mechanical ventilation exerts its detrimental effect is as of yet unknown, but it appears that overdistension of lung units or shear forces generated during repetitive opening and closing of atelectatic lung units exacerbates, or even initiates, significant lung injury and inflammation. The term "biotrauma" has recently been elaborated to describe the process by which stress produced by mechanical ventilation leads to the upregulation of an inflammatory response. For mechanical ventilation to exert its deleterious effect, cells are required to sense mechanical forces and activate intracellular signaling pathways able to communicate the information to its interior. This information must then be integrated in the nucleus, and an appropriate response must be generated to implement and/or modulate its response and that of neighboring cells. In this review, we present a perspective on ventilator-induced lung injury with a focus on mechanisms and clinical implications. We highlight some of the most recent findings, which we believe contribute to the generation and propagation of ventilator-induced lung injury, placing a special emphasis on their implication for future research and clinical therapies.
Epidermal cells cultured on a collagen-based material (1986)

Transmission electron microscopy is an effective means of characterizing the phenotypic expression of epidermal cells. Epidermal cells cultured on plastic dishes proliferate into several layers and differentiate in the same manner as in vivo. Epidermal cells may be cultured on a collagen-based material which can be used as a synthetic epidermis for wound coverage instead of a skin autograft. The purpose of this study is to characterize and compare the morphology of epidermal cells grown on plastic, collagen sheets, and collagen sponges under similar cell culture conditions.
Characterization of the Pharmacophore Properties of Novel Selective Estrogen Receptor Downregulators (SERDs) (2010)

Selective estrogen receptor (ER) down-regulators (SERDs) reduce ERalpha protein levels as well as block ER activity and therefore are promising therapeutic agents for the treatment of hormone refractory breast cancer. Starting with the triarylethylene acrylic acid SERD 4, we have investigated how alterations in both the ligand core structure and the appended acrylic acid substituent affect SERD activity. The new ligands were based on high affinity, symmetrical cyclofenil or bicyclo[3.3.1]nonane core systems, and in these, the position of the carboxyl group was extended from the ligand core, either retaining the vinylic linkage of the substituent or replacing it with an ether linkage. Although most structural variants showed binding affinities for ERalpha and ERbeta higher than that of 4, only the compounds preserving the acrylic acid side chain retained SERD activity, although they could possess varying core structures. Hence, the acrylic acid moiety of the ligand is crucial for SERD-like blockade of ER activities.
Immune therapy in inflammatory bowel disease and models of colitis (2001)

Immune therapies have altered the management of patients with inflammatory bowel disease. In future they will influence not only the indications for surgery but also its timing and outcome.
Detection and Quantitation of Serum Mesothelin, a Tumor Marker for Patients with Mesothelioma and Ovarian Cancer (2006)

We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.
Individual intestinal symbionts induce a distinct population of RORγ + regulatory T cells (2015)

T regulatory cells that express the transcription factor Foxp3 (Foxp3(+) T(regs)) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct T(reg) population in the mouse colon, which constrains immuno-inflammatory responses. This induction—which we find to map to a broad, but specific, array of individual bacterial species—requires the transcription factor Rorγ, paradoxically, in that Rorγ is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Rorγ's transcriptional footprint differs in colonic T(regs) and T(H)17 cells and controls important effector molecules. Rorγ, and the T(regs) that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Rorγ results in very different outcomes even in closely related cell types.
Finite-element methods for active contour models and balloons for 2-D and 3-D images (1993)

The use of energy-minimizing curves, known as "snakes" to extract features of interest in images has been introduced by Kass, Witkin and Terzopoulos (1987). A balloon model was introduced by Cohen (1991) as a way to generalize and solve some of the problems encountered with the original method. A 3-D generalization of the balloon model as a 3-D deformable surface, which evolves in 3-D images, is presented. It is deformed under the action of internal and external forces attracting the surface toward detected edgels by means of an attraction potential. We also show properties of energy-minimizing surfaces concerning their relationship with 3-D edge points. To solve the minimization problem for a surface, two simplified approaches are shown first, defining a 3-D surface as a series of 2-D planar curves. Then, after comparing finite-element method and finite-difference method in the 2-D problem, we solve the 3-D model using the finite-element method yielding greater stability and faster convergence. This model is applied for segmenting magnetic resonance images.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Following the fate of individual T cells throughout activation and clonal expansion. Signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative response. (1997)

A detailed understanding of the effects of costimulatory signals on primary T cell expansion has been limited by experimental approaches that measure the bulk response of a cell population, without distinguishing responses of individual cells. Here, we have labeled live T cells in vitro with a stable, fluorescent dye that segregates equally between daughter cells upon cell division, allowing the proliferative history of any T cell present or generated during a response to be monitored over time. This system permits simultaneous evaluation of T cell surface markers, allowing concomitant assessment of cellular activation and quantitative determination of T cell receptor (TCR) occupancy on individual cells. Through this approach, we find that TCR engagement primarily regulates the frequency of T cells that enter the proliferative pool, but has relatively little effect on the number of times these cells will ultimately divide. In contrast, CD28-costimulation regulates both the frequency of responding cells (particularly at sub-maximal levels of TCR engagement), and more prominently, the number of mitotic events that responding cells undergo. When CD28-stimulation is blocked, provision of IL-2 restores the frequency of responding cells and the normal pattern of mitotic progression, indicating that the other CD28-induced genes are not required for this effect. An unexpected finding was that even at maximal levels of TCR engagement and CD28-mediated costimulation, only 50-60% of the original T cells in culture can be induced to divide. The nondividing cells are heterogeneous for naive versus memory markers, suggesting a more complex relationship between expression of memory markers and the ability to be recruited into the dividing pool. From these studies, we conclude that a stringent checkpoint regulates the participation of activated T cells in clonal expansion, with TCR and CD28 signals having both overlapping and differential effects on the induction and maintenance of T cell responses.
Exchangeable gene trap using the Cre/mutated lox system. (1999)

The gene trap technique is a powerful approach for characterizing and mutating genes involved in mouse development. However, one shortcoming of gene trapping is the relative inability to induce subtle mutations. This problem can be overcome by introducing a knock-in system into the gene trap strategy. Here, we have constructed a new gene trap vector, pU-Hachi, employing the Cre-mutated lox system (Araki et al., 1997), in which a pair of mutant lox, lox71 and lox66, was used to promote targeted integrative reaction by Cre recombinase. The pU-Hachi carries splicing acceptor (SA)-lox71-internal ribosomal entry site (IRES)-beta-geo-pA-loxP-pA-pUC. By using this vector, we can carry out random insertional mutagenesis as the first step, and then we can replace the beta-geo gene with any gene of interest through Cre-mediated integration. We have isolated 109 trap clones electroporated with pU-Hachi, and analyzed their integration patterns by Southern blotting to select those carrying a single copy of the trap vector. By use of some of these clones, we have succeeded in exchanging the reporter gene at high efficiency, ranging between 20-80%. This integration system is also quite useful for plasmid rescue to recover flanking genomic sequences, because a plasmid vector sequence can be introduced even when the pUC sequence of the trap vector is lost through integration into the genome. Thus, this method, termed exchangeable gene trapping, has many advantages as the trapped clones can be utilized to express genes with any type of mutation.
Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection (2003)

3beta-Hydroxy-lup-20(29)-en-28-oic acid (betulinic acid) is a pentacyclic lupane-type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti-inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti-HIV-1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti-HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti-HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post-binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV-1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma-derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non-melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer.
DNA isolation from small tissue samples using salt and spermine (1991)

Journal Article DNA isolation from small tissue samples using salt and spermine Get access Jeffrey A. Ross, Jeffrey A. Ross Search for other works by this author on: Oxford Academic PubMed Google Scholar Garret B. Nelson, Garret B. Nelson 1Environmental Health Research and Testing, Inc.Research Triangle Park, NC 27709, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Katrina L. Holden Katrina L. Holden 1Environmental Health Research and Testing, Inc.Research Triangle Park, NC 27709, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 21, 11 November 1991, Page 6053, https://doi.org/10.1093/nar/19.21.6053 Published: 11 November 1991 Article history Received: 18 July 1991 Published: 11 November 1991
Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients (2015)

Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion.
New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia (2015)

Significant advances have been made in the last decade toward a better understanding of the disease pathogenesis and the development of novel therapies that target specific subsets of adult acute lymphoblastic leukemia (ALL). Risk-adapted strategies are transforming the disease treatment and prognosis. With current treatment regimens, long-term survival is achieved by approximately 50% of patients with B-cell ALL, 50% to 60% of patients with Philadelphia chromosome-positive ALL, and approximately 80% of patients with Burkitt's leukemia. Genomic profiling in ALL has identified new prognostic markers, new therapeutic targets, and novel ALL subtypes. These may be amenable to future targeted therapies that can further improve outcomes. The early recognition of early precursor T-cell ALL, a distinct pathobiological entity with a poor prognosis, is essential for the development of an effective clinical management strategy. The role of monoclonal antibodies and cytotoxic T-cell therapies continues to be defined. Many of the approaches are currently being evaluated for ALL salvage. Their incorporation into frontline adult ALL therapy, in concomitant or sequential strategies, may increase the cure rates to levels achieved in pediatric ALL and may reduce the need for prolonged intensive and maintenance chemotherapy.
Automated DC Offset Calibration Strategy for Structural Health Monitoring Based on Portable CW Radar Sensor (2014)

This paper introduces a strategy for automatically selecting dc offset calibration methods on a 2.4-GHz continuous wave (CW) radar sensor, which measures displacement for the purpose of structural health monitoring. Obtaining accurate displacement measurements using CW radar requires the successful application of dc offset calibration. This article compares four commonly applied dc offset calibration methods with a focus on each of the methods' accuracy and efficiency for different measurement signal characteristics. Simulation results are presented to evaluate the accuracy of each method. An advanced systematic strategy for selecting the most appropriate method based on signal characteristics is developed. The automated selection strategy is implemented in software and validated on experimental data.
Respiratory Syncytial Virus Modified by Deletions of the NS2 Gene and Amino Acid S1313 of the L Polymerase Protein Is a Temperature-Sensitive, Live-Attenuated Vaccine Candidate That Is Phenotypically Stable at Physiological Temperature (2012)

Human respiratory syncytial virus (RSV) is the leading viral cause of lower respiratory tract disease in infants and children worldwide. In previous work to develop point mutations in RSV with improved genetic stability, we observed that an attenuating mutation at amino acid position 1321 in the L polymerase protein was subject to deattenuation by a spontaneous second-site compensatory mutation at position 1313 (C. Luongo, C. C. Winter, P. L. Collins, and U. J. Buchholz, J. Virol. 86:10792-10804, 2012). In the present study, we found that deletion of position 1313 (Δ1313), irrespective of the presence of an attenuating mutation at position 1321, provided a new attenuating mutation. RSV bearing Δ1313 replicated in cell culture as efficiently as wild-type virus at 32°C, was restricted for replication at 37°C, and was restricted 50-fold and 150-fold in the upper and lower respiratory tracts, respectively, of mice. We combined the Δ1313 deletion with the previously described, attenuating NS2 gene deletion (ΔNS2) to produce the recombinant live-attenuated RSV vaccine candidate ΔNS2/Δ1313. During in vitro stress tests involving serial passage at incrementally increasing temperatures, a second-site compensatory mutation was detected in close proximity of Δ1313, namely, I1314T. This site was genetically and phenotypically stabilized by an I1314L substitution. Combination of I1314L with ΔNS2/Δ1313 yielded a virus, ΔNS2/Δ1313/1314L, with genetic stability at physiological temperature. This stabilized vaccine candidate was moderately temperature sensitive and had a level of restriction in chimpanzees comparable to that of MEDI-559, a promising RSV vaccine candidate that presently is in clinical trials but lacks stabilized attenuating mutations. The level of attenuation and genetic stability identify ΔNS2/Δ1313/1314L as a promising candidate for evaluation in pediatric phase I studies.
Monocular 3D scene understanding with explicit occlusion reasoning (2011)

Scene understanding from a monocular, moving camera is a challenging problem with a number of applications including robotics and automotive safety. While recent systems have shown that this is best accomplished with a 3D scene model, handling of partial object occlusion is still unsatisfactory. In this paper we propose an approach that tightly integrates monocular 3D scene tracking-by-detection with explicit object-object occlusion reasoning. Full object and object part detectors are combined in a mixture of experts based on their expected visibility, which is obtained from the 3D scene model. For the difficult case of multi-people tracking, we demonstrate that our approach yields more robust detection and tracking of partially visible pedestrians, even when they are occluded over long periods of time. Our approach is evaluated on two challenging sequences recorded from a moving camera in busy pedestrian zones and outperforms several state-of-the-art approaches.
Regulation of Synthesis of Some Proteinase Inhibitors in Human Hepatoma Cells HepG2 by Cytokines, Hepatocyte Growth Factor and Retinoic Acid (1993)

Subconfluent monolayers of human hepatoma HepG2 cells were cultured for 2 days in serum-free DMEM containing 1 microM dexamethasone and human recombinant hepatocyte growth factor (HGF), retinoic acid (RA), IL-1, IL-6, LIF and mixtures of these factors. Incorporation of labelled thymidine was significantly decreased by IL-6, IL-1 and HGF but only slightly by LIF and RA. Synthesis of acute phase proteins secreted daily to the media was measured by electroimmunoassay with monospecific antisera. In addition, the synthesis and secretion of some proteinase inhibitors (alpha-1-proteinase inhibitor, alpha-1-antichymotrypsin, C1-inactivator, plasminogen activator inhibitor-1, inter-alpha-trypsin inhibitor and pre-alpha-inhibitor) was evaluated by incorporation of labelled methionine and fluorography. Among the cytokines tested IL-6 was the most potent regulator of acute phase protein synthesis. Hepatocyte growth factor stimulated basal synthesis of alpha-1-antichymotrypsin, and to a lesser extent affected some other proteins. Retinoic acid preferentially increased synthesis of alpha-1-antichymotrypsin, ceruloplasmin and plasminogen activator inhibitor-1. Both HGF and RA slightly modulated cytokine-induced synthesis of several acute phase proteins in HepG2 cells.
Selection of Influenza Virus Mutants in Experimentally Infected Volunteers Treated with Oseltamivir (2001)

Volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) virus and treated with the neuraminidase (NA) inhibitor oseltamivir were monitored for the emergence of drug-resistant variants. Two (4%) of 54 resistant viruses were detected by NA inhibition assay among last-day isolates recovered from 54 drug recipients. They bore a substitution His274Tyr in the NA. Hemagglutinin (HA) variants detected in the placebo group differed from the egg-adapted inoculum virus by virtue of amino acid substitutions at residues 137, 225, or both. These variants had a higher affinity for Neu5Ac(alpha2-6)Gal-containing receptors, which are characteristic of human respiratory epithelium, than for Neu5Ac(alpha2-3)Gal-containing receptors, which are typical of chicken egg allantoic membrane. Although appearing to be more sensitive to oseltamivir in humans, the variants with increased affinity for Neu5Ac(alpha2-6)Gal receptors were less sensitive than the Neu5Ac(alpha2-3)Gal-binding variants in Madin-Darby canine kidney cells. Thus, HA affinity for receptors is an essential feature of influenza virus susceptibility to NA inhibitors, both in cell culture and in humans.