gebhart/patrepeval huggingface dataset:
In vivo inhibition by a site-specific catalytic RNA subunit of RNase P designed against the BCR-ABL oncogenic products: a novel approach for cancer treatment (2000)

One major obstacle to the effective treatment of cancer is to distinguish between tumor cells and normal cells. The chimeric molecules created by cancer-associated chromosomal abnormalities are ideal therapeutic targets because they are unique to the disease. We describe the use of a novel approach based on the catalytic RNA subunit of RNase P to destroy specifically the tumor-specific fusion genes created as a result of chromosome abnormalities. Using as a target model the abnormal BCR-ABL p190 and p210 products, we constructed M1-RNA with guide sequences that recognized the oncogenic messengers at the fusion point (M1-p190-GS and M1-p210-GS). To test the effectiveness and the specificity of M1-p190-GS and M1-p210-GS, we studied in vitro and in vivo effects of these RNA enzymes against BCR-ABL(p190) and BCR-ABL(p210), bearing in mind that both fusion genes share the ABL sequence but differ in the sequence coming from the BCR gene. We showed that M1-p190-GS and M1-p210-GS can act as sequence-specific endonucleases and can exclusively cleave target RNA that forms a base pair with the guide sequence (GS). We also demonstrated that when M1-p190-GS and M1-p210-GS were expressed in proper mammalian cell models, they abolished the effect of BCR-ABL by specifically decreasing the amount of the target BCR-ABL mRNA and preventing the function of the BCR-ABL oncogenes. These data clearly demonstrate the usefulness of the catalytic activity of M1-GS RNA to cleave specifically the chimeric molecules created by chromosomal abnormalities in human cancer and to represent a novel approach to cancer treatment.
Multimedia over ATM: progress, status and future (2002)

Multimedia is an emerging service which integrates voice, video and data in the same service. With the progress made in high speed large capacity multimedia servers, high speed networks, cost effective QoS, acceptable service category and cost effective set top boxes, it is currently possible to carry multimedia over high speed networks cost effectively and efficiently. This paper surveys the progress made and the future of efficiently carrying multimedia over ATM networks.
A 1.8-GHz LC VCO with 1.3-GHz tuning range and digital amplitude calibration (2005)

A 1.8-GHz LC VCO designed in a 0.18-/spl mu/m CMOS process achieves a very wide tuning range of 73% and measured phase noise of -123.5 dBc/Hz at a 600-kHz offset from a 1.8-GHz carrier while drawing 3.2 mA from a 1.5-V supply. The impacts of wideband operation on start-up constraints and phase noise are discussed. Tuning range is analyzed in terms of fundamental dimensionless design parameters yielding useful design equations. An amplitude calibration technique is used to stabilize performance across the wide band of operation. This amplitude control scheme not only consumes negligible power and area without degrading the phase noise, but also proves to be instrumental in sustaining the VCO performance in the upper end of the frequency range.
An Algorithm for Correction of Distortion of Laser Marking Systems (2007)

Images printed by laser marking systems will be distorted if linear voltages are given to the galvanometers due to the nonlinear relationship between angles of the galvanometers and coordinates of the image field. This paper presents a novel algorithm for correction of the distortion. A grid that covers the whole range of the image field is printed. The expected positions of the intersected points of the grid are calculated, and linear input voltages of the galvanometers are given to the laser marking system for printing the grid. Without distortion, the grid would be expected to be composed of vertical and horizontal lines. As a matter of fact, the printed lines will be curves. The intersected points of the curves are measured too. As any point to be printed will be in one of the quadrangles of the distorted grid, the corresponding corrected voltages of the galvanometers are calculated by linear interpolation according to the vertices of the quadrangle and their voltage inputs. Using the corrected voltages for printing, the distortion will be corrected. It is proved reliable by simulation and experiments on the laser marking system.
Cytotoxicity of Bovine Seminal Ribonuclease:  Monomer versus Dimer (2005)

Bovine seminal ribonuclease (BS-RNase) is a homologue of bovine pancreatic ribonuclease (RNase A). Unlike RNase A, BS-RNase has notable toxicity for human tumor cells. Wild-type BS-RNase is a homodimer linked by two intermolecular disulfide bonds. This quaternary structure endows BS-RNase with resistance to inhibition by the cytosolic ribonuclease inhibitor protein (RI), which binds tightly to RNase A and monomeric BS-RNase. Here, we report on the creation and analysis of monomeric variants of BS-RNase that evade RI but retain full enzymatic activity. The cytotoxic activity of these monomeric variants exceeds that of the wild-type dimer by up to 30-fold, indicating that the dimeric structure of BS-RNase is not required for cytotoxicity. Dimers of these monomeric variants are more cytotoxic than wild-type BS-RNase, suggesting that the cytotoxicity of the wild-type enzyme is limited by RI inhibition following dissociation of the dimer in the reducing environment of the cytosol. Finally, the cytotoxic activity of these dimers is less than that of the constituent monomers, indicating that their quaternary structure is a liability. These data provide new insight into structure-function relationships of BS-RNase. Moreover, BS-RNase monomers described herein are more toxic to human tumor cells than is any known variant or homologue of RNase A including Onconase, an amphibian homologue in phase III clinical trials for the treatment of unresectable malignant mesothelioma.
Physical and Functional HAT/HDAC Interplay Regulates Protein Acetylation Balance (2010)

The balance between protein acetylation and deacetylation controls several physiological and pathological cellular processes, and the enzymes involved in the maintenance of this equilibrium-acetyltransferases (HATs) and deacetylases (HDACs)-have been widely studied. Presently, the evidences obtained in this field suggest that the dynamic acetylation equilibrium is mostly maintained through the physical and functional interplay between HAT and HDAC activities. This model overcomes the classical vision in which the epigenetic marks of acetylation have only an activating function whereas deacetylation marks have a repressing activity. Given the existence of several players involved in the preservation of this equilibrium, the identification of these complex networks of interacting proteins will likely foster our understanding of how cells regulate intracellular processes and respond to the extracellular environment and will offer the rationale for new therapeutic approaches based on epigenetic drugs in human diseases.
An experimental comparison of autoregressive and Fourier-based descriptors in 2D shape classification (1995)

An experimental comparison of shape classification methods based on autoregressive modeling and Fourier descriptors of closed contours is carried out. The performance is evaluated using two independent sets of data: images of letters and airplanes. Silhouette contours are extracted from non-occluded 2D objects rotated, scaled, and translated in 3D space. Several versions of both types of methods are implemented and tested systematically. The comparison clearly shows better performance of Fourier-based methods, especially for images containing noise.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Application of nitric oxide and carbon monoxide in a model of renal preservation (2008)

The beneficial vasodilatory effects of CORM-3 during warm preservation improved renal function during reperfusion; SNP exerted similar, although less pronounced, effects.
IFN-α Enhances TLR3-Mediated Antiviral Cytokine Expression in Human Endothelial and Epithelial Cells by Up-Regulating TLR3 Expression (2005)

TLRs play a critical role in early innate immune response to virus infection. TLR3 together with TLR7 and TLR8 constitute a powerful system to detect genetic material of RNA viruses. TLR3 has been shown to bind viral dsRNA whereas TLR7 and TLR8 are receptors for viral single-stranded RNA. In this report we show that TLR7 or TLR8 are not expressed in human epithelial A549 cells or in HUVECs. Accordingly, A549 cells and HUVECs were unresponsive to TLR7/8 ligand R848. TLR3 was expressed at a higher level in HUVECs than in A549 cells. The TLR3 ligand poly(I:C) up-regulated IFN-beta, IL-28, IL-29, STAT1, and TLR3 expression in HUVECs but not in A549 cells. An enhanced TLR3 expression by transfection or by IFN-alpha stimulation conferred poly(I:C) responsiveness in A549 cells. Similarly, IFN-alpha pretreatment strongly enhanced poly(I:C)-induced activation of IFN-beta, IL-28, and IL-29 genes also in HUVECs. In conclusion, our results suggest that IFN-alpha-induced up-regulation of TLR3 expression is involved in dsRNA activated antiviral response in human epithelial and endothelial cells.
Different Pulse Shapes to Obtain Small Fiber Selective Activation by Anodal Blocking— A Simulation Study (2004)

The aim of this study was to investigate whether it is possible to reduce a charge per pulse, which is needed for selective nerve stimulation. Simulation is performed using a two-part simulation model: a volume conductor model to calculate the electrical potential distribution inside a tripolar cuff electrode and a human fiber model to simulate the fiber response to simulation. Selective stimulation is obtained by anodal block. To obtain anodal block of large fibers, long square pulses (> 350 micros) with a relatively high currents (1-2.5 mA) are usually required. These pulses might not be safe for a long-term application because of a high charge per pulse. In this study, several pulse shapes are proposed that have less charge per pulse compared with the conventional square pulse and would therefore be safer in a chronic application. Compared with the conventional square pulse, it was possible to reduce the charge with all proposed pulse shapes, but the best results are obtained with a combination of a square depolarizing pulse and a blocking pulse. The charge per pulse was up to 32% less with that pulse shape than with a square pulse. Using a hyperpolarizing anodal prepulse preceding a square pulse, it was not possible to block nerve fibers in a whole nerve bundle and to obtain reduction of a charge per phase. Reduction of the charge could be achieved only with spatially selective blocking. The charge per phase was larger for the combination of a hyperpolarizing anodal prepulse and a two-step pulse than for the two-step pulse alone.
Expression of Co-stimulatory 4-1BB Ligand Induces Significant Tumor Regression and Protective Immunity (1999)

Co-stimulatory molecules play an important role in initiating antitumor immune responses. Engineered tumor cells expressing co-stimulatory molecules have been used as cancer vaccines in both experimental tumor models and clinical trials. In this study, we cloned a cDNA gene coding for the mouse co-stimulatory molecule 4-1BBL by RTPCR. The expression vector pCI-4-1BBL was constructed by DNA recombinant technology and further transfected into a moderately immunogenic EL4 and a poorly immunogenic BL6-10 tumor cell line. Expression of the co-stimulatory molecule 4-1BBL is able to induce tumor regression of EL4/4-1BBL but not BL6-10/4-1BBL tumor cell line in syngeneic BALB/c mice. The tumor regression which is mainly mediated by CD8+ T cells further leads to protective immunity against the parental EL4 tumor. Our results thus indicate the potential utility of engineered tumor cells expressing co-stimulatory molecule 4-1BBL, especially in combination with other co-stimulatory molecules such as B7-1 in cancer vaccine.
Catalysis in Polysiloxane Gels: Platinum-Catalyzed Hydrosilylation of Polymethylhydrosiloxane Leading to Reusable Catalysts for Reduction of Nitroarenes (2009)

Novel polysiloxane gels, to which platinum species are encapsulated, are prepared by treatment of polymethylhydrosiloxane with alkenes in the presence of Karstedt's catalyst. These gels act as reusable catalysts in the reduction of functionalized nitroarenes with H(2) to the corresponding substituted anilines without leaking the catalyst species.
The dorsal root ganglion under attack: the acquired sensory ganglionopathies (2010)

Acquired sensory ganglionopathies--or sensory neuronopathies--are a rare type of peripheral neuropathy characterised by damage to the sensory nerve cell bodies in the dorsal root ganglia. Subacute or chronic in onset, sensory ganglionopathies typically present with a non-length dependent pattern of large fibre sensory loss. The causes of this distinct clinical picture include paraneoplastic syndromes, immune mediated diseases, infections, as well as drug, toxin and excess vitamin exposure. Here we discuss the clinical and pathological features of acquired sensory ganglionopathies and focus on a practical approach to their diagnosis and management.
FLT3 INHIBITORS: RECENT ADVANCES AND PROBLEMS FOR CLINICAL APPLICATION. (2015)

FLT3, a type III receptor tyrosine kinase, expresses on most acute leukemia cells as well as normal hematopoietic stem/progenitor cells. Mutation in the <i>FLT3</i> gene is the most frequent genetic alteration in acute myeloid leukemia (AML) and is well known as an important driver mutation for the development of myeloid malignancies. <i>FLT3</i> mutation is a strong poor prognostic factor for the long-term survival in AML patients, while neither high-dose chemotherapy nor allogeneic hematopoietic stem cell transplantation can overcome a poor prognosis. Development of an FLT3 inhibitor is, therefore, much awaited. To date, several potent FLT3 inhibitors have been developed and some of them were evaluated for efficacy in clinical trials, although no FLT3 inhibitor has been yet approved. Moreover, several problems for clinical use, such as adverse effects, blood concentration and resistance have been apparent. Recently developed AC220 is a highly selective and sensitive FLT3 inhibitor. In Phase I and II trials, AC220 so far showed the best efficacy of AML cells harboring <i>FLT3</i> mutation among clinically evaluated FLT3 inhibitors, while severe bone marrow suppression and QTc prolongation should be resolved for the clinical use. In this review, I summarize the characteristics of FLT3 inhibitors in clinical development and discuss important issues to be resolved for clinical use.
Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2 (2001)

The endothelial cell (EC) specific tyrosine kinase receptor, Tie2, interacts with at least two ligands, angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2). Ang1 stimulates Tie2 receptor autophosphorylation, while Ang2 has been reported to inhibit Ang1-induced Tie2 receptor autophosphorylation. We studied the effects of Ang1 and Ang2 in an in vitro model of angiogenesis. Human ECs (HUVEC), cultured on 3-D fibrin matrices, were treated with conditioned media (CM) from stably transfected cells expressing human Ang1 or Ang2, or with purified recombinant proteins. EC tube formation was measured as a differentiation index (DI), calculated as the ratio of total tube length over residual of EC monolayer. CM from Ang1 overexpressing A10 SMC or HEK293T cells induced profound HUVEC differentiation, resulting in the formation of extensive capillary-like tubes within 48 h (DI: 24.58+/-5.91 and 19.13+/-7.86, respectively) vs. control (DI: 2.73+/-1.68 and 2.15+/-1.45, respectively, both P<0.001). Interestingly, CM from two independent cell lines overexpressing Ang2 also produced a significant increase in EC differentiation (DI: 9.22+/-3.00 and 9.72+/-4.84, both P<0.005 vs. control) although the degree of angiogenesis was significantly less then that seen with Ang1. Addition of Ang1* (a genetically engineered variant of naturally occurring Ang1) or Ang2 also resulted in dose dependent increases in DI, which were blocked by an excess of soluble Tie2 receptor (20 microg/ml). Both Ang1* and Ang2 induced modest increases in [3H]thymidine incorporation into HUVECs (20 and 26%, respectively), which were inhibited by excess soluble Tie2. Although Ang2 was unable to induce significant Tie2 receptor phosphorylation during a 5-min exposure, a 24-h pretreatment with Ang2, followed by brief re-exposure, produced Tie2 phosphorylation in HUVEC comparable to that produced by Ang1*. These results demonstrate for the first time that Ang2 may have a direct role in stimulating Tie2 receptor signaling and inducing in vitro angiogenesis. Our findings suggest that the physiological role of Ang2 is more complex than previously recognized: acting alternately to promote or blunt Tie2 receptor signaling in endothelial cells, depending on local conditions.
Regulation of DMD pathology by an ankyrin-encoded miRNA (2011)

These studies demonstrate a link for miR-486 as a regulator of the PTEN/AKT pathway in dystrophin-deficient muscle and an important factor in the regulation of DMD muscle pathology.
The control of cardiovascular shunts in the fetal and perinatal period (1988)

The fetal circulation has two major vascular shunts, the ductus arteriosus and the ductus venosus. The ductus arteriosus connects the pulmonary artery with the descending portion of the aortic arch, hence shunting most of the right ventricular output away from the unexpanded lungs. The ductus venosus connects instead the portal sinus with the inferior vena cava and allows well-oxygenated umbilical vein blood to bypass the liver and reach the central circulation rapidly. Both blood vessels cease their function after birth and undergo permanent closure. It is now well established that prenatal patency of the ductus arteriosus is an active state sustained by a prostaglandin. A similar mechanism has been recently recognized in the fetal ductus venosus. Evidence is presented indicating that prostaglandin E2 and prostaglandin I2 are natural relaxants, respectively, for the ductus arteriosus and the ductus venosus. In addition, both vascular shunts share the dependence on an endogenous cytochrome P-450 mechanism to develop their contractile tone. This mechanism may be important in the normal process of shunt closure at birth. While broadening the knowledge of fetal cardiovascular homeostasis, advances in this field have important implications for the prevention and management of certain pathological conditions affecting the newborn.
Molecular Profile of theBCL2Family of the Apoptosis Related Genes in Breast Cancer Cells after Treatment with Cytotoxic/Cytostatic Drugs (2008)

BCL2 (bcl-2) gene family members are important regulators of apoptosis. Increasing evidence supports their modulated expression in breast cancer cells and in many cases their relation to chemotherapy response, outcome, and overall prognosis, as well as their value as important potent therapeutic targets. Investigation and increased understanding of their transcriptional regulation and their specific roles in cancer progression and therapy response will be useful for focusing research on the development of novel therapies targeted against this gene family members' expression status. In the present review, we describe current knowledge of the molecular profile of the classical and novel members of the BCL2 family of genes as a response of breast cancer cells to cytotoxic/cytostatic drugs.
An Efficient and Versatile Mammalian Viral Vector System for Major Histocompatibility Complex Class I/Peptide Complexes (2002)

ABSTRACT We report a Sendai virus (SeV) vector system for expression of major histocompatibility complex (MHC) class I/peptide complexes. We cloned the extracellular domain of a human MHC class I heavy chain, HLA-A*2402, and human β-2 microglobulin (β2m) fused with HLA-A*2402-restricted human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte (CTL) epitopes (e-β2m) in separate SeV vectors. When we coinfected nonhuman mammalian cells with the SeVs, naturally folded human MHC class I/peptide complexes were secreted in the culture supernatants. Biotin binding peptide sequences on the C terminus of the heavy chain were used to tetramerize the complexes. These tetramers made in the SeV system recognized specific CD8-positive T cells in peripheral blood mononuclear cells of HIV-1-positive patients with a specificity and sensitivity similar to those of MHC class I tetramers made in an Escherichia coli system. Solo infection of e-β2m/SeV produced soluble e-β2m in the culture supernatant, and cells pulsed with the soluble protein were recognized by specific CTLs. Furthermore, when cells were infected with e-β2m/SeV, these cells were recognized by the specific CTLs more efficiently than the protein pulse per se. SeV is nonpathogenic for humans, can transduce foreign genes into nondividing cells, and may be useful for immunotherapy to enhance antigen-specific immune responses. Our system can be used not only to detect but also to stimulate antigen-specific cellular immune responses.
A Macrophage Invasion Mechanism of Pathogenic Mycobacteria (1997)

Tuberculosis is the leading cause of death due to an infectious organism, killing an estimated 3 million people annually. Mycobacterium tuberculosis, the causative agent of tuberculosis, and other pathogenic mycobacteria require entry into host macrophages to initiate infection. An invasion mechanism was defined that was shared among pathogenic mycobacteria including M. tuberculosis, M. leprae, and M. avium but not by nonpathogenic mycobacteria or nonmycobacterial intramacrophage pathogens. This pathway required the association of the complement cleavage product C2a with mycobacteria resulting in the formation of a C3 convertase. The mycobacteria-associated C2a cleaved C3, resulting in C3b opsonization of the mycobacteria and recognition by macrophages.
Effect of pretreatment with thiopental and phenytoin on postischemic brain damage in rabbits (1979)

Thiopental (10 mg/kg iv and 10 mg/kg im), phenytoin (15 mg/kg iv), and placebo were given to three groups of 12 anesthetized rabbits each before a pneumatic tourniquet was placed around the neck and inflated to 250 mm Hg for 20 min. No pulsations were noted in the retinal or auricular arteries, and the EEG was flattened during this period. Neurological evaluations performed subsequently showed that significantly greater deficits were seen in the groups receiving thiopental or placebo than in the group receiving phenytoin at 15 and 30 min after tourniquet release. This same trend, though of lesser magnitude, was again observed at 72 hours. Histological examination of the brains, obtained 72 hours postischemia, showed necrotic injuries occurring in 42% of the animals receiving placebo, 8% of those given thiopental, and in none of the phenytoin group (p < 0.01). Evidence of ischemic lesions was noted in 33, 42, and 33% of these same groups, respectively. Pretreatment with phenytoin appeared to protect against ischemic cerebral lesions, as evidenced by both neurological recovery and postmortem findings.