gebhart/patrepeval huggingface dataset:
Interleukin-5 (IL-5) Augments the Progression of Liver Fibrosis by Regulating IL-13 Activity (2006)

Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic Schistosoma mansoni infection. Although infection intensities were similar in C57BL/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4+ Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.
Nicotinic acid– and monomethyl fumarate–induced flushing involves GPR109A expressed by keratinocytes and COX-2–dependent prostanoid formation in mice (2010)

The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of monomethyl fumarate. Here we analyzed the mechanisms underlying GPR109A-mediated flushing and show that both Langerhans cells and keratinocytes express GPR109A in mice. Using cell ablation approaches and transgenic cell type-specific GPR109A expression in Gpr109a-/- mice, we have provided evidence that the early phase of flushing depends on GPR109A expressed on Langerhans cells, whereas the late phase is mediated by GPR109A expressed on keratinocytes. Interestingly, the first phase of flushing was blocked by a selective cyclooxygenase-1 (COX-1) inhibitor, and the late phase was sensitive to a selective COX-2 inhibitor. Both monomethyl fumarate and nicotinic acid induced PGE2 formation in isolated keratinocytes through activation of GPR109A and COX-2. Thus, the early and late phases of the GPR109A-mediated cutaneous flushing reaction involve different epidermal cell types and prostanoid-forming enzymes. These data will help to guide new efficient approaches to mitigate nicotinic acid-induced flushing and may help to exploit the potential antipsoriatic effects of GPR109A agonists in the skin.
Osteopontin Expression by Osteoclast and Osteoblast Progenitors in the Murine Bone Marrow: Demonstration of Its Requirement for Osteoclastogenesis and Its Increase After Ovariectomy* (1997)

Osteoclast development requires cell-to-cell contact between hematopoietic osteoclast progenitors and bone marrow stromal/osteoblastic support cells. Based on this, we hypothesized that osteopontin, an adhesion protein produced by osteoclasts and osteoblasts, plays a role in osteoclastogenesis. Using in situ hybridization, we demonstrate that cells expressing the osteopontin messenger RNA (mRNA) appear after 3 days of culturing murine bone marrow cells. The number of these cells increases thereafter, reaching a peak on day 5. In the same cultures, cells expressing alkaline phosphatase (AP) or tartrate resistant acid phosphatase (TRAP), phenotypic markers for osteoblastic and osteoclast-like cells, respectively, appeared subsequent to the appearance of the osteopontin-positive cells. By means of a combination of in situ hybridization and histostaining, it was shown that the osteopontin mRNA was localized in 30-50% of the AP-positive or the TRAP-positive, as well as in nonspecific esterase (NSE)-positive, cells. The number of cells expressing both the osteopontin mRNA and either one of the three phenotypic markers was significantly increased in bone marrow cultures from estrogen-deficient mice, as compared with controls. Conversely, the number of all three populations of double positive cells was decreased in cultures treated with a specific antimouse rabbit osteopontin antibody or an RGD peptide. These findings indicate that osteopontin is expressed during the early stages of the differentiation of osteoclast and osteoblast progenitors in the bone marrow and that its cell adhesion properties are required for osteoclastogenesis.
DREZ Coagulations for Deafferentation Pain Related to Spinal and Peripheral Nerve Lesions: Indication and Results of 79 Consecutive Procedures (1997)

During a 16 years' period, a total of 79 dorsal root entry zone coagulations were performed in 68 patients for deafferentation pain. Of the 23 patients who underwent surgery for pain due to cervical root avulsion, 18 (82%) had a good (12) or fair (6) pain relief (mean follow-up period 51 months). Twelve (57%) patients with spinal cord injuries noted continuous pain reduction (10 good, 2 fair; mean follow-up 52 months). Continuous marked improvement for longer periods was reported only by 2 out of 10 patients with postherpetic neuralgia and 1 out of 7 patients with painful states due to other brachial plexus lesions and none out of 5 with spinal cord lesions (3) and phantom limb pain (2).
A Novel Approach for Intracellular 3D Immuno‐Labeling for Electron Tomography (2012)

Electron tomography (ET) is an indispensable high-resolution tool for three dimensional (3D) imaging in cell biology. When applied to immuno-labeled cells, ET can provide essential insights in both the cellular architecture and the dynamics. Current protocols for 3D immuno-labeling of intracellular antigens include permeabilization steps that cause random, extensive cell membrane disruption. This permeabilization results in a poor cell ultrastructure, limiting the usefulness of the specimens for high-resolution studies. Here we describe a novel method, based on a well-controlled permeabilization by targeted laser cell perforation, that allows for the 3D immuno-localization of cytoplasmic antigens in cultured cells. The approach is unique since it is applicable to both chemically and cryo-fixed cells and leads to a superior ultrastructural preservation for electron microscopy and tomography.
Cardioversion of Atrial Arrhythmias: Audit of Anticoagulation Management (1997)

Patients undergoing cardioversion for chronic atrial fibrillation should receive anticoagulation for three weeks before and four weeks after the procedure. Patients with atrial flutter and acute atrial fibrillation are also at risk of thromboembolic complications, so they too should be anticoagulated for cardioversion. Of the 36 acutely admitted patients who were cardioverted, 18 were in atrial fibrillation and 18 in atrial flutter. All except three of those in fibrillation were anticoagulated with heparin before cardioversion, but only seven received warfarin after cardioversion. Of those in flutter, 10 received heparin and eight received no anticoagulation before cardioversion. One patient underwent transoesophageal echocardiography before cardioversion to exclude atrial thrombi. Only two patients received warfarin for a month after cardioversion. Of the 20 elective cardioversions, 10 were in atrial fibrillation and 10 in atrial flutter. Five of those in fibrillation had received at least three weeks' treatment with warfarin before cardioversion and two underwent transoesophageal echocardiography; the other three received either up to two hours of heparin or no anticoagulation before cardioversion. Only five patients received warfarin for a month after cardioversion. Nine of those in flutter received a few hours of heparin before cardioversion and one was not anticoagulated; none underwent transoesophageal echocardiography or received warfarin after cardioversion. The results of this audit demonstrate that anticoagulation for atrial arrhythmias was inconsistent and often inadequate. A formal anticoagulation policy for cardioversion has now been adopted.
Cellular Immunotherapy of Malignancies Using the Clonal Natural Killer Cell Line NK-92 (2001)

For years activated natural killer (A-NK) cells have been explored with respect to their efficacy in anticancer therapy, but, except for some anectdotal reports, no clear clinical benefit has been shown. However, as the understanding about the interactions of NK cells and tumor cells advances, the use of A-NK cells might be revisited with more sophisticated approaches that pay tribute to mechanisms which allow tumor cells to escape immune surveillance. Here the highly cytotoxic NK cell line NK-92 seems to be an attractive alternative for use in adoptive immunotherapy, because it was shown to exhibit substantial antitumor activity against a wide range of malignancies in vitro as well as in xenografted SCID mice. NK-92 cells are characterized by an almost complete lack of killer cell immunglobulin-like receptors (KIRs) yet conserved ability to perforin and granzyme B-mediated cytolytic activity, which make them unique among the few established NK and T cell-like cell lines. NK-92 is the only natural killer cell line that has entered clinical trials. Here we discuss the current status of development of this cell line for adoptive immunotherapy (AIT) of malignancies and review our first clinical experience in patients with advanced cancer who have received repeated transfusions of irradiated NK-92 in a phase I/II trial. Also we discuss issues that address safety aspects of immunotherapy with clonal cell lines and describe further manipulations, which hold the potential of significantly improving the clinical outcome of AIT with NK-92.
Magnetic smart material application to adaptive x-ray optics (2010)

We discuss a technique of shape modification that can be applied to thin walled (&#126;100-400 micron thickness) electroformed replicated optics or slumped glass optics to improve the near net shape of the mirror as well as the midfrequency ripple. The process involves sputter deposition of a magnetic smart material (MSM) film onto a permanently magnetic material. The MSM material exhibits strains about 400 times stronger than ordinary ferromagnetic materials. The deformation process involves a magnetic write head which traverses the surface, and under the guidance of active metrology feedback, locally magnetizes the surface to impart strain where needed. Designs and basic concepts as applied to space borne X-ray optics will be described.
Pattern structures for news clustering (2015)

Usually web search results are represented as long list of document snippets. It is difficult for users to navigate through this collection of text. We propose clustering method that uses pattern structure constructed on augmented syntactic parse trees. In addition, we compare our method to other clustering methods and demonstrate the limitations of the competitive methods.
Cysteine scanning mutagenesis of the N‐terminal 32 amino acid residues in the lactose permease of Escherichia coli (1994)

Using a functional lactose permease mutant devoid of Cys residues (C-less permease), each amino acid residue in the hydrophilic N-terminus and the first putative transmembrane helix was systematically replaced with Cys (from Tyr-2 to Trp-33). Twenty-three of 32 mutants exhibit high lactose accumulation (70-100% or more of C-less), and an additional 8 mutants accumulate to lower but highly significant levels. Surprisingly, Cys replacement for Gly-24 or Tyr-26 yields fully active permease molecules, and permease with Cys in place of Pro-28 also exhibits significant transport activity, although previous mutagenesis studies on these residues suggested that they may be required for lactose transport. As expected, Cys replacement for Pro-31 completely inactivates, in agreement with previous findings indicating that "helix-breaking" propensity at this position is necessary for full activity (Consler TG, Tsolas O, Kaback HR, 1991, Biochemistry 30:1291-1297). Twenty-nine mutants are present in the membrane in amounts comparable to C-less permease, whereas membrane levels of mutants Tyr-3-->Cys and Phe-12-->Cys are slightly reduced, as judged by immunological techniques. Dramatically, mutant Phe-9-->Cys is hardly detectable when expressed from the lac promoter/operator at a relatively low rate, but is present in the membrane in a stable form when expressed at a high rate from the T7 promoter. Finally, studies with N-ethylmalemide show that 6 Cys-replacement mutants that cluster at the C-terminal end of putative helix I are inactivated significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Incorporatinga priorianatomical information into image reconstruction in electrical impedance tomography (1999)

Image reconstruction in electrical impedance tomography using the sensitivity theorem is generally based on the assumption that the initial conductivity distribution of the body being imaged is uniform. The technique of image reconstruction using this method is described and reconstructed images are presented. Improvements in image quality and accuracy are demonstrated when accurate a priori 'anatomical' information, in the form of a model of the distribution of conductivity within the region to be imaged, is used to construct the sensitivity matrix. In practice correct a priori information is not available, for example the conductivity values within the various anatomical regions will not be known. An iterative algorithm is presented which allows the conductivity parameters of the a priori model to be determined during reconstruction.
Macrophage-Parasite Interactions in Leishmania Infections (1990)

Macrophages have different roles in Leishmania infections. They function as host-cells to the parasite, they present parasite antigens to the immune system, and they also act as effector cells responsible for parasite killing in the healing stages of the infection. Protein and carbohydrate ligands on the parasite surface, which interact with receptors on the macrophage membrane during phagocytosis, have been identified. Survival of Leishmania in its host cell requires a metabolic adaptation to the intracellular environment. The nutritional requirements of the microorganism must be satisfied and the deleterious effect of oxygen metabolites and of lysosomal hydrolases must be adequately counteracted. When a successful immune response develops, macrophages become activated and acquire the capacity to destroy the microorganism. Possible reasons why these mechanisms fail in certain individuals or experimental host-parasite combinations are discussed.
Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states (2009)

Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.
Mechanism for Nanotube Formation from Self-Bending Nanofilms Driven by Atomic-Scale Surface-Stress Imbalance (2007)

We demonstrate, by theoretical analysis and molecular dynamics simulation, a mechanism for fabricating nanotubes by self-bending of nanofilms under intrinsic surface-stress imbalance due to surface reconstruction. A freestanding Si nanofilm may spontaneously bend itself into a nanotube without external stress load, and a bilayer SiGe nanofilm may bend into a nanotube with Ge as the inner layer, opposite of the normal bending configuration defined by misfit strain. Such rolled-up nanotubes can accommodate a high level of strain, even beyond the magnitude of lattice mismatch, greatly modifying the tube electronic and optoelectronic properties.
Cell Biology Volume 3 Ed. 3 (2005)

This four-volume laboratory manual contains comprehensive state-of-the-art protocols essential for research in the life sciences. Techniques are presented in a friendly step-by-step fashion, providing useful tips and potential pitfalls. The important steps and results are beautifully illustrated for further ease of use. This collection enables researchers at all stages of their careers to embark on basic biological problems using a variety of technologies and model systems. This thoroughly updated third edition contains 165 new articles in classical as well as rapidly emerging technologies. Topics covered include: * Cell and Tissue Culture: Associated Techniques, Viruses, Antibodies, Immunocytochemistry (Volume 1) * Organelle and Cellular Structures, Assays (Volume 2) * Imaging Techniques, Electron Microscopy, Scanning Probe and Scanning Electron Microscopy, Microdissection, Tissue Arrays, Cytogenetics and In Situ Hybridization, Genomics and Transgenic Knockouts and Knock-down Methods (Volume 3) * Transfer of Macromolecules, Expression Systems, Gene Expression Profiling (Volume 4)
Formation of Alkanethiol Monolayer on Ge(111) (2001)

Alkanethiols, CH3(CH2)(n-1)SH, are shown to react readily with HF-treated Ge(111) surface at room temperature to form a high-quality monolayer. The resulting films are characterized by using contact angle analysis (CAA), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE), and high-resolution electron energy loss spectroscopy (HREELS). The octanethiol and octadecanethiol films on Ge(111) both exhibit 101 degrees and 40 degrees water and hexadecane contact angles, respectively. These values indicate that the thiol surface coverage is relatively high, and that the films possess a high degree of orientational ordering. The angle-resolved XPS analysis supports that thiols are bound to the Ge surface by Ge-S bonds at the monolayer/Ge interface. The film thickness values obtained by XPS and SE agree well with the earlier reported values on alkyl monolayers on Ge(111) prepared by Grignard reaction. On the basis of HREEL spectra taken after thermal annealing steps, the monolayers are found to be thermally stable up to 450 K. The thermal stability provides further evidence that thiols are covalently bonded to Ge(111).
Comparison of Cockroach Traps and Attractants for Monitoring German Cockroaches (Dictyoptera: Blattellidae) (2006)

Studies were conducted in large arenas and simulated kitchens to compare the effectiveness of eight traps (seven sticky traps and one jar trap) and ve attractants for monitoring German cockroaches (Blattella germanica L.). The evaluated traps were Trapper (type 9110 1), Catchmaster 150, 1001, and 2881, Victor-M330, Victor-M327, Glue board in D-Sect station, and a baby food jar trap. In choice tests, Victor-M330 consistently caught the most and Catchmaster 150 caught the fewest cockroaches. Numbers in the Victor-M330 were 78-and 36-fold greater than in the Catchmaster 150 in the large arena and simulated kitchen experiments, respectively. Sticky traps caught proportionally more small nymphs than large nymphs. Baby food jar trap samples had signicantly greater adult/total ratio and large nymph/nymph ratios than the sticky trap samples. In addition, baby food jar trap catches had signicantly lower male/adult ratio than Catchmaster 1001 and Victor-M327 trap catches. Flat Trapper traps caught signicantly more cockroaches than the assembled (triangular) Trapper traps. Bread with beer, peanut butter, Trapper roach attractant, NAF430 gel bait, and Invite lure were compared in choice tests for their effect on sticky trap catches in simulated kitchens. All attractants signicantly increased the number of cockroaches trapped in sticky traps compared with an unbaited trap. Bread with beer was by far the most attractive bait, increasing trap catches by 34-fold over the unbaited control. Baited sticky traps may have much greater efcacy than nonbaited traps for monitoring and controlling German cockroach infestations.
Asimetría regulatoria, equidad y transición a la competencia en las telecomunicaciones españolas (1999)

The patient is a 52-year-old man with schizophrenia who developed severe, unremitting gingival pain after his ziprasidone dosage was increased from 80 to 120 mg. His physical examination and laboratory findings were unremarkable. He did not have any extra-pyramidal side effects. His pain did not ameliorate after taking acetaminophen and non-steroidal anti-inflammatory drugs. As a last resort, the patient took benztropine and his pain subsided within half an hour. His ziprasidone dosage was decreased and the patient is currently doing well. He has not experienced gingival pain since his medication was adjusted.
Microrobotic cell injection (2002)

Advances in microbiology demonstrate the need for manipulating individual biological cells, such as for cell injection which includes pronuclei injection and intracytoplasmic injection. Conventionally, cell injection has been conducted manually. In this paper, we present a microrobotic system capable of performing automatic embryo pronuclei DNA injection autonomously and semi-autonomously through a hybrid visual servoing control scheme. After injection, the DNA injected embryos were transferred into a pseudopregnant foster female mouse to reproduce transgenic mice for cancer studies. Experimental results show that the injection success rate was 100%. The system setup, hybrid control scheme and other important issues in this application, such as automatic focusing, are discussed.
Optimization of a Novel Series of Ataxia-Telangiectasia Mutated Kinase Inhibitors as Potential Radiosensitizing Agents (2015)

We previously reported a novel inhibitor of the ataxia-telangiectasia mutated (ATM) kinase, which is a target for novel radiosensitizing drugs. While our initial lead, compound 4, was relatively potent and nontoxic, it exhibited poor stability to oxidative metabolism and relatively poor selectivity against other kinases. The current study focused on balancing potency and selectivity with metabolic stability through structural modification to the metabolized site on the quinazoline core. We performed extensive structure-activity and structure-property relationship studies on this quinazoline ATM kinase inhibitor in order to identify structural variants with enhanced selectivity and metabolic stability. We show that, while the C-7-methoxy group is essential for potency, replacing the C-6-methoxy group considerably improves metabolic stability without affecting potency. Promising analogues 20, 27g, and 27n were selected based on in vitro pharmacology and evaluated in murine pharmacokinetic and tolerability studies. Compound 27g possessed significantly improve pharmacokinetics relative to that of 4. Compound 27g was also significantly more selective against other kinases than 4. Therefore, 27g is a good candidate for further development as a potential radiosensitizer.