gebhart/patrepeval huggingface dataset:
ATP-Binding Cassette Transporter G1 Negatively Regulates Thymocyte and Peripheral Lymphocyte Proliferation (2009)

Cholesterol is a key component of cell membranes and is essential for cell growth and proliferation. How the accumulation of cellular cholesterol affects lymphocyte development and function is not well understood. We demonstrate that ATP-binding cassette transporter G1 (ABCG1) regulates cholesterol homeostasis in thymocytes and peripheral CD4 T cells. Our work is the first to describe a cell type in Abcg1-deficient mice with such a robust change in cholesterol content and the expression of cholesterol metabolism genes. Abcg1-deficient mice display increased thymocyte cellularity and enhanced proliferation of thymocytes and peripheral T lymphocytes in vivo. The absence of ABCG1 in CD4 T cells results in hyperproliferation in vitro, but only when cells are stimulated through the TCR. We hypothesize that cholesterol accumulation in Abcg1(-/-) T cells alters the plasma membrane structure, resulting in enhanced TCR signaling for proliferation. Supporting this idea, we demonstrate that B6 T cells pretreated with soluble cholesterol have a significant increase in proliferation. Cholesterol accumulation in Abcg1(-/-) CD4 T cells results in enhanced basal phosphorylation levels of ZAP70 and ERK1/2. Furthermore, inhibition of ERK phosphorylation in TCR-stimulated Abcg1(-/-) T cells rescues the hyperproliferative phenotype. We describe a novel mechanism by which cholesterol can alter signaling from the plasma membrane to affect downstream signaling pathways and proliferation. These results implicate ABCG1 as an important negative regulator of lymphocyte proliferation through the maintenance of cellular cholesterol homeostasis.
FoxO proteins in pancreatic β-cells as potential therapeutic targets in diabetes (2008)

Diabetes results from complete (Type 1) or progressive (Type 2) insulin insufficiency. Resulting chronic and acute hyperglycemia are thus prevented mainly by insulin injections, a therapy that is care intensive, costly and does not abolish vascular damage, with severe consequences for the patient in the long term. In view of the epidemic spread of the disease, diabetes is considered a major threat for public healthcare systems. Thus, there is a great incentive to find therapies and drugs preserving or restoring pancreatic β-cells mass and function. In this context, this review addresses the FoxO transcription factors as direct or indirect, in vivo or ex vivo drug targets, since FoxO proteins play a central role for β-cells growth and resistance to oxidative stress. The review includes specific proposals for preclinical drug development.
Complex Distribution, Not Absolute Amount of Adiponectin, Correlates with Thiazolidinedione-mediated Improvement in Insulin Sensitivity (2004)

Adiponectin is an adipocyte-specific secretory protein that circulates in serum as a hexamer of relatively low molecular weight (LMW) and a larger multimeric structure of high molecular weight (HMW). Serum levels of the protein correlate with systemic insulin sensitivity. The full-length protein affects hepatic gluconeogenesis through improved insulin sensitivity, and a proteolytic fragment of adiponectin stimulates beta oxidation in muscle. Here, we show that the ratio, and not the absolute amounts, between these two oligomeric forms (HMW to LMW) is critical in determining insulin sensitivity. We define a new index, S(A), that can be calculated as the ratio of HMW/(HMW + LMW). db/db mice, despite similar total adiponectin levels, display decreased S(A) values compared with wild type littermates, as do type II diabetic patients compared with insulin-sensitive individuals. Furthermore, S(A) improves with peroxisome proliferator-activated receptor-gamma agonist treatment (thiazolidinedione; TZD) in mice and humans. We demonstrate that changes in S(A) in a number of type 2 diabetic cohorts serve as a quantitative indicator of improvements in insulin sensitivity obtained during TZD treatment, whereas changes in total serum adiponectin levels do not correlate well at the individual level. Acute alterations in S(A) (DeltaS(A)) are strongly correlated with improvements in hepatic insulin sensitivity and are less relevant as an indicator of improved muscle insulin sensitivity in response to TZD treatment, further underscoring the conclusions from previous clamp studies that suggested that the liver is the primary site of action for the full-length protein. These observations suggest that the HMW adiponectin complex is the active form of this protein, which we directly demonstrate in vivo by its ability to depress serum glucose levels in a dose-dependent manner.
Bilateral Arteriovenous Shunts as a Method for Evaluating Tissue-Engineered Vascular Grafts in Large Animal Models (2017)

There remains a need for large animal models to evaluate tissue-engineered vascular grafts (TEVGs) under arterial pressure to provide preclinical data for future potential human clinical trials. We present a comprehensive method for the interrogation of TEVGs, using an ovine bilateral arteriovenous (AV) shunt implantation model. Our results demonstrate that this method can be performed safely without complications, specifically acute heart failure, steal syndrome, and hypoxic brain injury, and it is a viable experimental paradigm. Our method allows for a non-invasive evaluation of TEVGs in terms of graft flow, graft diameter, and graft patency, while also allowing for graft needle puncture under ultrasound guidance. In addition, traditional pathological analysis, histology, and immunohistochemistry may be performed with the contralateral side providing paired control data to eliminate inter-subject variability while reducing the total number of animals. Further, we present a review of existing literature of preclinical evaluation of TEVGs in large animal models as AV conduits.
Self-sterilizing and self-cleaning of silicone catheters coated with TiO2 photocatalyst thin films: A preclinical work (2001)

TiO(2) photocatalysts were successfully coated on silicone catheters or medical tubes by pretreatment of the silicone surface with a sulfuric acid solution (5 M) for 3 h. The TiO(2) film adhered to the silicone substrate strongly against tensile and bending stresses. On the TiO(2)-coated silicone-catheters under UV illumination, both the bleaching of methylene blue dye and the photocatalytic bactericidal effect on Escherichia coli (E. coli) cells were confirmed. Thus, this type of catheter can be sterilized and cleaned simply by irradiation with low-intensity UV light and can, therefore, be useful in the protection from catheter-related bacterial infections.
Error Recognition and Feedback with Lexical Functional Grammar (2003)

This paper describes the error recognition module of an interactive ICALL system with a special focus on the underlying grammar theory. Using the system, language learners are invited to produce complete written sentences in small question-answer dialogs with the computer. This setting challenges learners to use language interactively in order to enhance the development of communicative competence. Emphasis is put on the possibility of giving adequate feedback to the learner if a syntactically ill formed sentence is encountered. It is argued that the theory of Lexical Functional Grammar (LFG) is well suited to be used in the parsing and error recognition module of the system as well as to provide intelligent feedback to learners. The concepts and structures used in LFG closely resemble the descriptive knowledge of language learners about a language, and, therefore, the results of an automatic analysis can easily be translated from a computationally tractable form to language easily understood by the learner.
Feline Hypertrophic Cardiomyopathy: A Spontaneous Large Animal Model of Human HCM (2017)

Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from <i>in vitro</i> and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients.
Large‐scale production of monoclonal antibodies in suspension culture (1988)

Monoclonal antibodies are being manufactured for clinical trials in suspension culture at the 1300-L scale. Suspension culture offers some advantages relative to high-density mammalian cell culture methods; in particular, the ability to closely monitor the behavior of cells in a homogeneous environment. Computer control and on-line mass spectrography of exit gases provide instantaneous information about the culture metabolic activity. Air sparging and agitation by marine impeller provide aeration sufficient to maintain a constant dissolved oxygen tension at cell concentrations up to 5.0 x 10(6) cells/mL without causing apparent cell damage.
A 1-Megapixel, progressive-scan image sensor with antiblooming control and lag-free operation (1991)

A 1024-pixel*1024-pixel interline charge-coupled device (IL CCD) image sensor has been developed. It incorporates antiblooming and electronic exposure control while eliminating lag and obtaining a high responsivity. The novel features of this device include a noninterlaced, or progressive-scan, architecture and dual-horizontal registers that can be used to clock out the image area by one or two lines at a time. These features make it well suited for applications demanding high-resolution-image capture from a single, high-speed scan. The progressive-scan architecture of this device covers the same resolution in an electronic-camera application as that of a 2-million-element, interlaced device.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Parametrically Amplified $Z$-Axis Lorentz Force Magnetometer (2011)

This paper describes a microelectromechanical systems (MEMS) Lorentz force navigation magnetometer whose fabrication is fully compatible with existing foundry processes used to manufacture MEMS inertial sensors. Operating at 1 atm, the magnetometer is shown to have a Brownian-noise-limited field resolution of 87 nT/√Hz and a corresponding angular resolution of 0.7°/√Hz. To achieve Brownian-noise-limited performance at 1 atm, parametric amplification was performed which amplifies the Lorentz force 40% more than the Brownian noise force and increases the field sensitivity of the device up to 82.5 folds. Here, the parametric signal is also used to perform electromechanical amplitude modulation to mitigate capacitive feedthrough of the drive signal to the sensing electronics.
Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro (2005)

Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.
Combined immunization with fusion genes of mutated E7 gene of human papillomavirus type 16 did not enhance antitumor effect (2005)

We constructed highly immunogenic fusions of HPV16 E7 and E7GGG with mouse HSP70.1. Furthermore, we substantially enhanced protection against TC-1/A9 cells with downregulated MHC class I expression by doubling the pBSC/E7GGG.GUS dose, but we failed to demonstrate a beneficial effect of any combination of two fusion genes with different mechanisms causing enhancement of HPV16 E7 immunogenicity.
Oligopyrrole Synthesis by 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Bissulfonyl Ethylenes (2007)

One by one or two by two: In a general approach to the iterative construction of oligopyrroles, the cycloaddition of azomethine ylides derived from pyrrolyl α-iminoesters with 1,2-bis(phenylsulfonyl)ethylene is followed by the elimination of the sulfonyl groups in situ under basic conditions. This strategy is amenable to the introduction of one or two pyrrole units in each iterative cycle. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z703258_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Enhanced surface acoustic wave cell sorting by 3D microfluidic-chip design (2017)

We demonstrate an acoustic wave driven microfluidic cell sorter that combines advantages of multilayer device fabrication with planar surface acoustic wave excitation. We harness the strong vertical component of the refracted acoustic wave to enhance cell actuation by using an asymmetric flow field to increase cell deflection. Precise control of the 3-dimensional flow is realized by topographical structures implemented on the top of the microchannel. We experimentally quantify the effect of the structure dimensions and acoustic parameter. The design attains cell sorting rates and purities approaching those of state of the art fluorescence-activated cell sorters with all the advantages of microfluidic cell sorting.
Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the Yersinia pseudotuberculosis tyrosine phosphatase (1995)

Suppression of host-cell-mediated immunity is a hallmark feature of Yersinia pseudotuberculosis infection. To better understand this process, the interaction of Y. pseudotuberculosis with macrophages and the effect of the virulence plasmid-encoded Yersinia tyrosine phosphatase (YopH) on the oxidative burst was analyzed in a chemiluminescence assay. An oxidative burst was generated upon infection of macrophages with a plasmid-cured strain of Y. pseudotuberculosis opsonized with immunoglobulin G antibody. Infection with plasmid-containing Y. pseudotuberculosis inhibited the oxidative burst triggered by secondary infection with opsonized bacteria. The tyrosine phosphatase activity of YopH was necessary for this inhibition. These results indicate that YopH inhibits Fc receptor-mediated signal transduction in macrophages in a global fashion. In addition, bacterial protein synthesis was not required for macrophage inhibition, suggesting that YopH export and translocation are controlled at the posttranslational level.
Tumor-Associated Macrophages as Target for Antitumor Therapy (2017)

It is well known that the microenvironment of solid tumors is rich in inflammatory cells that influence tumor growth and development. Macrophages, called tumor-associated macrophages (TAMs), are the most abundant immune cell population present in tumor tissue. Several studies have demonstrated that the density of TAMs is associated with a poor prognosis and positively correlates with tumor growth. Several studies have proved that TAMs may activate and protect tumor stem cells, stimulate their proliferation as well as promote angiogenesis and metastasis. Furthermore, TAMs-derived cytokines and other proteins, such as CCL-17, CCL-22, TGF-β, IL-10, arginase 1, and galectin-3, make a significant contribution to immunosuppression. Since TAMs influence various aspects of cancer progression, there are many attempts to use them as a target for immunotherapy. The numerous studies have shown that the primary tumor growth and the number of metastatic sites can be significantly decreased by decreasing the population of macrophages in tumor tissue, for example, by blocking recruitment of monocytes or eliminating TAMs already present in the tumor tissue. Moreover, there are attempts at reprogramming TAMs into proinflammatory M1 macrophages or neutralizing the protumoral products of TAMs. Another approach uses TAMs for anticancer drug delivery into the tumor environment. In this review, we would like to summarize the clinical and preclinical trials that were focused on macrophages as a target for anticancer therapies.
Batch manufacturing: Six strategic needs (1995)

Since the advent of industrial digital control systems in the mid-1970s, industry has had the promise of integrated, configurable digital batch control systems to replace the morass of electromechanical devices like relays and stepping switches, recorders, and indicators which comprised the components of previous generations of batch control systems - the {open_quotes}monolithic monsters{close_quotes} of the 1960s and earlier. To help fulfill that promise, there have been many wide-ranging proprietary automation solutions for batch control since 1975, many of them technically excellent. However, even the best examples suffered from the lack of a common language and unifying concept permitting separate systems to be interconnected and work together. Today, some 20 years after the digital revolution began, industry has microprocessors, memory chips, data highways, and other marvelous technology to help automate the control of discontinuous processes. They also are on the way to having an accepted standard for batch automation, ISA S88. Batching systems are at once conceptually simple but executionally complex. The notion of adding ingredients one at a time to a vat, mixing, and then processing into final form is as old as the stone age. Every homemaker on earth, male or female, is familiar with how to follow amore » recipe to create some sumptuous item of culinary delight. Food recipes, so familiar and ubiquitous, are really just microcosms of the S88 recipe standard. They contain the same components: (1) Header (name and description of item being prepared, sometimes serving size); (2) Formula (list and amount of ingredients); (3) Equipment requirements (pans, mixing and cooking equipment); (4) Procedure (description of order of ingredient addition, mixing and other processing steps, baking/cooling time, and other processing steps); and (5) Other information (safety, cautions, and other miscellaneous instructions).« less
Hyperbranched Polyesters Based on Adipic Acid and Glycerol (2004)

Abstract Summary: Hyperbranched polyesters with controlled molecular weights and properties have been prepared by an A 2 + B 3 approach by reacting glycerol and adipic acid without any solvents in the presence of tin catalysts. The hyperbranched polyesters have been evaluated by size exclusion chromatography (SEC) analysis and NMR spectroscopy in order to determine molecular weights and degrees of branching. Idealized structure of the hyperbranched polyesters synthesized here from adipic acid and glycerol in the presence of tin catalysts. image Idealized structure of the hyperbranched polyesters synthesized here from adipic acid and glycerol in the presence of tin catalysts.
Lung Cancer Screening with CT: Mayo Clinic Experience (2003)

CT can depict early-stage lung cancers. The rate of benign nodule detection is high.
Excessive tumor-elaborated VEGF and its neutralization define a lethal paraneoplastic syndrome (2001)

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and key regulator of both physiologic and pathologic (e.g., tumor) angiogenesis. In the course of studies designed to assess the ability of constitutive VEGF to block tumor regression in an inducible RAS melanoma model, mice implanted with VEGF-expressing tumors sustained high morbidity and mortality that were out of proportion to the tumor burden. Documented elevated serum levels of VEGF were associated with a lethal hepatic syndrome characterized by massive sinusoidal dilation and endothelial cell proliferation and apoptosis. Systemic levels of VEGF correlated with the severity of liver pathology and overall clinical compromise. A striking reversal of VEGF-induced liver pathology and prolonged survival were achieved by surgical excision of VEGF-secreting tumor or by systemic administration of a potent VEGF antagonist (VEGF-TRAP(R1R2)), thus defining a paraneoplastic syndrome caused by excessive VEGF activity. Moreover, this VEGF-induced syndrome resembles peliosis hepatis, a rare human condition that is encountered in the setting of advanced malignancies, high-dose androgen therapy, and Bartonella henselae infection. Thus, our findings in the mouse have suggested an etiologic role for VEGF in this disease and may lead to diagnostic and therapeutic options for this debilitating condition in humans.
Carotenoid based bio-compatible labels for third harmonic generation microscopy (2012)

The use of carotenoids as biologically friendly labels for third harmonic generation (THG) microscopy is demonstrated. Carotenoid containing liposomes are used to label cell structures via liposome cell fusion. The THG microscopy labels, called harmonophores, were characterized by measuring the third-order nonlinear susceptibility (χ((3))) of carotenoids: violaxanthin, neoxanthin, lutein, β-carotene, zeaxanthin, canthaxanthin and astaxanthin. The THG ratio method was used, which is based on measuring the THG intensity from two interfaces using a nonlinear optical microscope. The second hyperpolarizability values of carotenoids were extracted from χ((3)) measurements taking into account the refractive index at fundamental and third harmonic wavelengths. The length dependence of the second hyperpolarizability of conjugated polyenes from 9 to 13 double bonds with varying oxygen functional groups was investigated. It appears that the presence of epoxides can have a higher influence than an additional conjugated double bond. Furthermore, labelling of both Drosophila Schneider 2 cells and Drosophila melanogaster larvae myocytes with β-carotene was achieved. This study demonstrates that THG enhancement by carotenoids can be used for nontoxic in vivo labelling of subcellular structures for third harmonic generation microscopy.
Isolation and characterization of an equine rotavirus (1983)

A rotavirus, designated as the H-1 strain, was isolated from a diarrheic foal in primary African green monkey kidney cells and MA104 cells. This cell culture-adapted strain hemagglutinated erythrocytes of human group O, rhesus monkeys, guinea pigs, and sheep. It was found to be similar, if not identical, to porcine rotaviruses (strains OSU, EE, and A-580) by plaque reduction neutralization and hemagglutination inhibition tests, and, in addition, it was found to belong to subgroup 1. This equine rotavirus has an RNA electrophoretic migration pattern which was distinct from those of the three strains of porcine rotavirus. The serological relationship established by plaque reduction neutralization and hemagglutination inhibition tests between the equine (H-1) and porcine (OSU, EE, and A-580) rotaviruses is an example of a rotavirus of the same serotype being isolated from different species. The H-1 strain was distinct from four human rotavirus serotypes (Wa, DS-1, P, and St. Thomas 4) as well as from bovine rotavirus NCDV, simian rotavirus MMU18006, and canine rotavirus CU-1 by plaque reduction neutralization tests. This equine isolate (H-1) was found to be related antigenically to canine CU-1 and bovine NCDV rotaviruses in a one-way fashion by hemagglutination inhibition tests.