gebhart/patrepeval huggingface dataset:
Megakaryoblastic Leukemia 1, a Potent Transcriptional Coactivator for Serum Response Factor (SRF), Is Required for Serum Induction of SRF Target Genes (2003)

Megakaryoblastic leukemia 1 (MKL1) is a myocardin-related transcription factor that we found strongly activated serum response element (SRE)-dependent reporter genes through its direct binding to serum response factor (SRF). The c-fos SRE is regulated by mitogen-activated protein kinase phosphorylation of ternary complex factor (TCF) but is also regulated by a RhoA-dependent pathway. The mechanism of this pathway is unclear. Since MKL1 (also known as MAL, BSAC, and MRTF-A) is broadly expressed, we assessed its role in serum induction of c-fos and other SRE-regulated genes with a dominant negative MKL1 mutant (DN-MKL1) and RNA interference (RNAi). We found that DN-MKL1 and RNAi specifically blocked SRE-dependent reporter gene activation by serum and RhoA. Complete inhibition by RNAi required the additional inhibition of the related factor MKL2 (MRTF-B), showing the redundancy of these factors. DN-MKL1 reduced the late stage of serum induction of endogenous c-fos expression, suggesting that the TCF- and RhoA-dependent pathways contribute to temporally distinct phases of c-fos expression. Furthermore, serum induction of two TCF-independent SRE target genes, SRF and vinculin, was nearly completely blocked by DN-MKL1. Finally, the RBM15-MKL1 fusion protein formed by the t(1;22) translocation of acute megakaryoblastic leukemia had a markedly increased ability to activate SRE reporter genes, suggesting that its activation of SRF target genes may contribute to leukemogenesis.
Toward the Back-Up of Boceprevir (SCH 503034): Discovery of New Extended P4-Capped Ketoamide Inhibitors of Hepatitis C Virus NS3 Serine Protease with Improved Potency and Pharmacokinetic Profiles (2009)

Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P(4) pocket and optimization of the P(1)' capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P(4)-capped inhibitors were also found to have improved PK profile.
Uterine EMG analysis: a dynamic approach for change detection and classification (2000)

Toward the goal of detecting preterm birth by characterizing events in the uterine electromyogram (EMG), we propose a method of detection and classification of events in this signal. Uterine EMG is considered as a nonstationary signal and our approach consists of assuming piecewise stationarity and using a dynamic change detector with no a priori knowledge of the parameters of the hypotheses on the process state to be detected. The detection approach is based on the dynamic cumulative sum (DCS) of the local generalized likelihood ratios associated with a multiscale decomposition using wavelet transform. This combination of DCS and multiscale decomposition was shown to be very efficient for detection of both frequency and energy changes. An unsupervised classification based on the comparison between variance-covariance matrices computed from selected scales of the decomposition was implemented after detection. Finally a class labeling based on neural networks was developed. This algorithm of detection-classification-labeling gives satisfactory results on uterine EMG: in most cases more than 80% of the events are correctly detected and classified whatever the term of gestation.
Classroom Oral Reading and its Needs or Restraints (1989)

Few deny the beneficial effects of prose or poetry read aloud by a fluent and expressive reader; imparting reassurance, delivering entertainment, dispensing information or explanation, arousing curiosity, diffusing inspiration (Trelease, 1982). Apart from these advantages as we shall see, oral reading has the capability to engender literacy among individuals, more particularly our schoolchildren (Hoffman, 1982).
Ion distribution functions in an Ar-Cl ECR discharge (2000)

In processing plasmas, the ion distribution functions are generally non-Maxwellian and spatially varying. We have used the NRL axisymmetric particle simulation code QUASI-rz to calculate ion distribution functions at various positions in the plasma, for an ECR discharge in Ar/Cl gas mixture. We show that the distribution functions are determined by an interplay of several processes: ion acceleration due to the diverging magnetic field, or to the pre-sheath electric field, charge-exchange collisions, and Coulomb collisions between ions. Omitting any of these processes from a model radically alters the conclusions.
Multicard: An Open Hypermedia System (Demonstration). (1992)

This study revealed important differences in efficacy of commonly used pro- and anticoagulant drugs in children with end-stage liver disease undergoing liver transplantation. Therefore, dose adjustments of these drugs may be required. The results of this study may be helpful in the development of urgently needed protocols for strategies to prevent and treat bleeding and thrombotic complications in pediatric liver transplantation.
Upregulation of aquaporin-2 water channel expression in chronic heart failure rat. (1997)

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.
Reversal of Myocardial Injury Using Genetically Modulated Human Skeletal Myoblasts in a Rodent Cryoinjured Heart Model (2005)

Myoblasts carrying of hVEGF165 are potential therapeutic transgene carriers for cardiac repair.
Optimizing DNA transduction by selection of mutations that evade bacterial defense systems (2018)

We recently developed a platform where phage-transducing particles optimize DNA delivery to a wide range of hosts. Here, we use this platform to optimize DNA transduction into hosts that naturally restrict specific DNA sequences. We first show that a specific plasmid is restricted for transduction into a particular Salmonella strain. Using the platform, we select for a mutated plasmid that overcomes the restriction barrier. Insertion of the non-mutated sequence into a permissive plasmid restricts transduction. We further show that epigenetic modification enables the DNA to evade restriction by the putative defense system. Our results validate this straightforward genetic approach for optimization of DNA transduction into new hosts.
Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2- incompatible transplanted SCID mice (1994)

In a previous study, we found that total body irradiation (TBI) was essential to induce acute graft-versus-host disease (GVHD) after allogeneic H-2-incompatible splenocyte (SP) transplantation in SCID mice. SCID mice (H-2d) conditioned with cyclophosphamide and transplanted intravenously (IV) with 5 x 10(7) C57BL/6 (H-2b) SP developed chronic GVHD within 3 months posttransplant without any evidence of preceding acute GVHD. In this study, SCID mice were conditioned with 4 Gy TBI or non-TBI regimens, either BuCy2 (busulfan 4 mg/kg/d + cyclophosphamide 100 mg/kg/d for 2 days) or Cy5 (cyclophosphamide 100 mg/kg/d for 5 days), and then transplanted IV with 5 x 10(7) SP. The TBI-conditioned mice were further divided into tree transplant groups: (1) TBI and SP administered the same day (TBI + D0 SP), (2) SP administered 4 days post-TBI (TBI + D4 SP), and (3) SP administered 7 days post-TBI (TBI + D7 SP). The severity of GVHD was compared among these groups by clinical and histologic grading. Twenty-eight of 28 mice treated with TBI + D0 SP died of acute GVHD, with overwhelming diarrhea by day 15 posttransplantation. Sixteen mice treated with either TBI + D4 SP or TBI + D7 SP developed acute GVHD, but none of them died of this disorder during 30 days posttransplantation. The mice conditioned with non-TBI regimens developed chronic GVHD within 3 months without showing any detectable signs of acute GVHD. Serum and in situ colonic cytokines were determined by enzyme-linked immunosorbent assay and immunohistology respectively. TBI itself significantly increased both serum and colonic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and IL-6 when compared with non-TBI regimens and normal controls. TNF-alpha appeared in the serum and colon 4 hours post-TBI and peaked in 24 hours, followed by increasing IL-1 alpha and then IL-6 levels. TNF-alpha and IL-1 alpha decreased rapidly within 3 to 5 days post-TBI if no allogeneic cells were transplanted. Histoincompatible transplantation augmented cytokine release, which remained elevated on day 10 in these animals. Mice treated with TBI + D0 SP developed the most severe acute GVHD and had the highest levels of TNF-alpha, IL-1 alpha, and IL-6. The BuCy2-conditioned mice had the lowest cytokine levels and developed no acute GVHD. When the mice transplanted with TBI + D0 SP were treated immediately with recombinant soluble human TNF receptor (rhuTNFR:Fc) 100 micrograms/d intraperitoneally and for the subsequent 15 days acute GVHD mortality was significantly reduced from 100% to 50% (P < .001).(ABSTRACT TRUNCATED AT 400 WORDS)
Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE (2012)

SLE is an autoimmune inflammatory disease in which various pro- and anti-inflammatory cytokines, including TGF-β, IL-10, BAFF, IL-6, IFN-α, IFN-γ, IL-17, and IL-23, play crucial pathogenic roles. Virtually, all these cytokines can be generated by both innate and adaptive immune cells and exert different effects depending on specific local microenvironment. They can also interact with each other, forming a complex network to maintain delicate immune homeostasis. In this paper, we elaborate on the abnormal secretion and functions of these cytokines in SLE, analyze their potential pathogenic roles, and probe into the possibility of them being utilized as targets for therapy.
Isolate-dependent use of claudins for cell entry by hepatitis C virus (2013)

These findings highlight differential CLDN usage by HCV isolates, which may evolve based on variable expression of CLDN proteins in human liver cells. Broad CLDN tropism may facilitate viral escape from CLDN1-specific therapeutic strategies.
Donor–Acceptor Segregated Paracyclophanes Composed of Naphthobipyrrole and Stacked Fluoroarenes (2013)

The expeditious synthesis of donor-acceptor segregated paracyclophanes has been achieved by a selective SNAr reaction of hexafluorobenzene with o-dipyrrolylbenzenes and subsequent cyclodehydrogenation. An orthogonally arranged D-A segregated structure was confirmed by X-ray crystallography. The combined results of DFT calculations and absorption spectra revealed the charge transfer (CT) nature from the naphthobipyrrole (donor) to the stacked fluoroarene moiety (acceptor).
Safe Administration of the Measles Vaccine to Children Allergic to Eggs (1995)

The MMR vaccine can be safely administered in a single dose to children with allergy to eggs, even those with severe hypersensitivity.
Effect of vitamin E and copper on the vitamin E status and performance of growing pigs. (1991)

A 13-wk trial was conducted with 32 pigs to determine the effects of dietary Cu (250 ppm) and α-tocopheryl acetate (ATA, 22 IU/kg) on the performance, serum enzymes, serum and tissue tocopherols, and antibody production in growing pigs. Pigs were fed corn-soybean meal diets containing 21% CP the first 4 wk and 18% CP during the rest of the trial. All feed was stored a minimum of 14 d before it was fed. The addition of Cu decreased (P < .01) the concentration of α-tocopherol in the feed. α-Tocopherol concentrations were < .01 mg/kg in the starter diet and < 2 mg/kg in the grower diet after 14 d of storage. Supplemental Cu or ATA had no effect on ADG, feed intake, or gain:feed during the first 4 wk. During wk 5 to 13, the addition of Cu to diets containing no ATA increased daily feed intake and decreased gain:feed, but with ATA addition, feed intake decreased and gain:feed increased, resulting in a Cu × ATA interaction (P < .05). The addition of Cu or ATA had no effect (P > .1) on serum glutathione peroxidase or lactic dehydrogenase activity. Serum tocopherols were reduced (P < .05) by the addition of Cu during wk 1 to 4, 6 (P < .01), and 7 (P < .05) and increased (P < .01) by ATA addition during the entire experiment. The addition of ATA increased the tocopherol concentrations in bile, ham, heart, pancreas, kidney, spleen, liver, psoas and longissimus muscle (P < .01), kidney fat, backfat, and adrenal gland (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Accuracy of link capacity estimates using passive and active approaches with CapProbe (2004)

CapProbe is an inexpensive and accurate means to estimate capacity. CapProbe combines both dispersion and end-to-end delay to estimate the capacity of the narrowest link on a path. We evaluate in this paper the accuracy of CapProbe estimation, and its dependence on end systems speed, packet sizes, narrow link speeds, and other system parameters. We test kernel and user level implementations of CapProbe and find the kernel implementation to be much more accurate. We also evaluate through experiments the effect of probing packet size on the accuracy of CapProbe estimation. Finally, we explore the idea of a "passive CapProbe" within the context of a TCP flow. Passive here means that the dispersion and delay observed for the TCP flow data and ACK packets, without introducing any additional probing packets. We test active and passive versions of CapProbe with TCP. The active version is found to produce more accurate capacity estimates than the passive version.
Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study (2008)

Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated. All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance. Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids). Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity. Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity.
Office visits for otitis media: United States, 1975-90. (1992)

Data from the National Ambulatory Medical Care Survey show a steady increase in the number and rate of physician office visits for otitis media over the period from 1975 to 1990. The annual visit rate during this period more than doubled, and for children under age 15, increased 175 percent. Though the increase is greatest for males under age 2, there are substantial increases for males and females under age 15. Reasons for this dramatic increase are not readily apparent. Data from the National Health Interview Survey (NHIS), however, suggest that the increased visit rate may reflect an increase in the incidence of ear infections. According to NHIS data, the incidence of acute ear infections among the U.S. population increased by about 40 percent between 1982 and 1990, from 6.1 to 8.6 conditions per 100 persons per year. This compares with an increase of about 52 percent in the physician office visit rate for otitis media, from 1980 to 1990. (Because of gaps in data collection, it is not possible to compare precisely concurrent time periods.) The under 15 age group, which accounts for about 80 percent of otitis media physician office visits, experienced a 60 percent increase in office visit rate from 1980 to 1990. This parallels data from the NHIS that show a 60 percent increase in the incidence of acute ear infections among the under 17 age group from 1982 to 1990. The reporting of an acute ear infection in the NHIS does not necessarily equate to an incidence of otitis media, but the parallel increases in ear infection incidence and otitis media physician visits are mutually supportive and likely to be related.
All about different art (2010)

The work of the artist Kandinsky has enormous potential as a springboard for developing children′s art. As well as providing a host of opportunities for appraising and comparing, many of his paintings can be used to explore specific elements such as line, shape and colour.
Fast polarization self-modulation in a vertical-cavity surface-emitting laser (2002)

For many applications, it is important to modulate a semiconductor laser at very high rates (/spl ges/ tens GHz). Recently, a technique based on the self-modulation of the polarization in an edge-emitting semiconductor laser was used for generating high frequency optical pulses without requiring high-speed electronics. In this paper, a demonstration of polarization self-modulation using a vertical-cavity surface-emitting laser (VCSEL) is presented. VCSELs exhibit different intrinsic polarization properties from edge-emitting lasers are particularly well suited for two dimensional array applications including optical interconnection and optical storage.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Two highly conserved glutamic acid residues in the predicted β propeller domain of dipeptidyl peptidase IV are required for its enzyme activity (1999)

Dipeptidyl peptidase IV (DPP IV) is a member of the prolyl oligopeptidase family and modifies the biological activities of certain chemokines and neuropeptides by cleaving their N-terminal dipeptides. This paper reports the identification and possible significance of a novel conserved sequence motif Asp-Trp-(Val/Ile/Leu)-Tyr-Glu-Glu-Glu (DW(V/I/L)YEEE) in the predicted beta propeller domain of the DPP IV-like gene family. Single amino acid point mutations in this motif identified two glutamates, at positions 205 and 206, as essential for the enzyme activity of human DPP IV. This observation suggests a novel role in proteolysis for residues of DPP IV distant from the Ser-Asp-His catalytic triad.
Monoclonal Antibodies to Metacyclic Stage Antigens of Trypanosoma Cruzi * (1985)

Hybridoma cell lines secreting monoclonal antibodies against the Tulahuén strain of Trypanosoma cruzi were produced by the fusion of SP2/O-Ag 14 myeloma cells with spleen cells from mice immunized with irradiated metacyclic trypomastigotes. Twenty of the monoclonals synthesized by the hybridomas were identified as IgM, 2 as IgG1, 10 as IgG2a, 3 as IgG2b, 4 as IgG3, 1 as IgE, and 1 as IgA. Twenty-three of these antibodies had kappa light chains and 18 showed delta chains. Twelve of the monoclonals agglutinated metacyclic trypomastigotes without additional concentration and 4 of these precipitated antigens in extracts of T. cruzi metacyclic or epimastigote stages. One monoclonal precipitated an epimastigote antigen, while another reacted with a metacyclic antigen, and 2 antibodies formed precipitin lines with antigens of both stages. Agglutinin assays performed to characterize surface antigenic specificities of the 12 monoclonal antibodies showed that 2 reacted only with the metacyclic stage of the Tulahuén strain. Two monoclonals agglutinated both metacyclic trypomastigotes and epimastigotes of the Tulahuén strains. Three antibodies caused clumping of metacyclics and epimastigotes of the Tulahuén, Raccoon V, and Corpus Christi strains of T. cruzi, while a fourth also reacted with bloodstream trypomastigotes. One monoclonal detected identical epitopes on metacyclics and epimastigotes of T. cruzi and epimastigotes of Trypanosoma musculi, while 2 antibodies reacted with metacyclics, epimastigotes, and bloodstream trypomastigotes of the Tulahuén and Raccoon V strains and the bloodstream stage of T. musculi. One antibody agglutinated all stages and strains of T. cruzi, T. musculi, and Trypanosoma lewisi which were tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with AIDS and AIDS-related complex. (1990)

We tried to assess the long-term safety and potential efficacy of passive immunization in AIDS-related-complex (ARC) and AIDS patients. We also wanted to establish whether hyperimmune plasma from healthy human immunodeficiency virus 1 (HIV-1)-infected individuals clears the cell-free virus from circulation. Using the polymerase chain reaction (PCR), we were able to provide conclusive evidence that hyperimmune plasma is effective and maintains long-term neutralization of viremia. Using the cell test, we found that in most patients the total antibody level was maintained; in one of the ARC patients, it actually increased 8-fold and has remained at that level for nearly 2 years. The CD4+ cell count decreased in the AIDS patients but was stable in the ARC patient. Clinically, there was an initial improvement in all patients, but five of six of the advanced/terminal AIDS patients had died by month 17. Our studies suggest that passive immunization may be safe in ARC and AIDS patients. It reduces HIV-1 viremia to levels undetectable even by PCR. To advanced/terminal patients, the benefit is of limited duration, while to ARC patients it may be long-term. Therefore, passive immunization should start early in the disease.