gebhart/patrepeval huggingface dataset:
Abstract A146: Stromal neuregulin-1 modulates the response to MEK inhibitors in WT BRAF/WT NRAS (WT/WT) melanomas (2018)

Abstract MEK-ERK1/2 signaling is elevated in the majority of melanomas. While MEK inhibitors (MEKi) are FDA-approved for mutant BRAF melanoma, and have some activity against NRAS mutant tumors, they have shown little activity in patients with melanomas that are wild type for BRAF and NRAS (WT/WT). Since the tumor microenvironment (TME) often regulates drug resistance, we tested the effects of growth factors on WT/WT melanoma growth in the presence of MEKi. Neuregulin-1 (NRG1) protected patient-derived WT/WT human melanoma cell lines from growth inhibition mediated by trametinib (MEKi). Phospho-proteomic analysis and clinical grade neutralizing antibodies implicated adaptive activation of ErbB3/ErbB2 complexes in the protective effects of NRG1. NRG1 was detected in fibroblasts and cancer-associated fibroblasts (CAF), and CAF-conditioned medium activated ErbB3/ErbB2 signaling in MEK inhibited WT/WT melanoma cells. ErbB3 and ErbB2 neutralizing antibodies blocked the protective effects of fibroblast- and CAF-derived NRG1 in vitro and cooperated with MEKi to delay xenograft growth in vivo. Together our results provide a rationale for the treatment of WT/WT melanomas with the combination of MEKi and anti-ErbB3/ErbB2 antibodies. Citation Format: Claudia Capparelli, Timothy J. Purwin, Shea Heilman, Inna Chervoneva, Michael A. Davies, Jeffrey E. Gershenwald, Andrew E. Aplin. Stromal neuregulin-1 modulates the response to MEK inhibitors in WT BRAF/WT NRAS (WT/WT) melanomas [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A146.
Endotoxin-induced mortality in rats is reduced by nitrones. (1989)

The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF, and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.
The Art of Forecasting: Shaping the Future of School Social Work (1996)

Journal Article The Art of Forecasting: Shaping the Future of School Social Work Get access Edith M. Freeman, PhD, ACSW Edith M. Freeman, PhD, ACSW Professor School of Social Welfare, University of Kansas, Lawrence Search for other works by this author on: Oxford Academic Google Scholar Children & Schools, Volume 18, Issue 3, July 1996, Pages 131–134, https://doi.org/10.1093/cs/18.3.131 Published: 01 July 1996
MP3 and AAC Explained (1999)

This paper explains the basic technology and some of the special features of MPEG1 /2 Layer-3 (aka MP3). It also sheds some light on the factors determining the quality of compressed audio and what can be done wrong in MPEG encoding and decoding. WhyMPEG-1Layer-3?
PR72, a novel regulator of Wnt signaling required for Naked cuticle function (2005)

The Wnt signaling cascade is a central regulator of cell fate determination during embryonic development, whose deregulation contributes to oncogenesis. Naked cuticle is the first Wnt-induced antagonist found in this pathway, establishing a negative-feedback loop that limits the Wnt signal required for early segmentation. In addition, Naked cuticle is proposed to function as a switch, acting to restrict classical Wnt signaling and to activate a second Wnt signaling pathway that controls planar cell polarity during gastrulation movements in vertebrates. Little is known about the biochemical function of Naked cuticle or its regulation. Here we report that PR72, a Protein Phosphatase type 2A regulatory subunit of unknown function, interacts both physically and functionally with Naked cuticle. We show that PR72, like Naked cuticle, acts as a negative regulator of the classical Wnt signaling cascade, establishing PR72 as a novel regulator of the Wnt signaling pathway. Our data provide evidence that the inhibitory effect of Naked cuticle on Wnt signaling depends on the presence of PR72, both in mammalian cell culture and in Xenopus embryos. Moreover, PR72 is required during early embryonic development to regulate cell morphogenetic movements during body axis formation.
Elevated levels of nerve growth factor in the thalamus and spinal cord of rats affected by experimental allergic encephalomyelitis. (1995)

In a previous study it was shown that the levels of NGF in the cerebrospinal fluid of patients affected by multiple sclerosis (MS) increase during the acute phase of the disease and decrease in the remission phase. In the present study, using an animal model of MS, we investigate whether any changes in NGF levels occur in brains of rats affected by Experimental Allergic Encephalomyelitis (EAE). The results show an enhanced level of NGF in the thalamus and spinal cord and a numerical increase of mast cells (MCs) expressing mRNA-NGF localized in these two regions. These observations suggest that NGF is involved in EAE and that MCs contribute to the local increase of NGF.
Expression Cloning of a Protective Leishmania Antigen (1995)

Parasite-specific CD4+ T cells have been shown to transfer protection against Leishmania major in susceptible BALB/c mice. An epitope-tagged expression library was used to identify the antigen recognized by a protective CD4+ T cell clone. The expression library allowed recombinant proteins made in bacteria to be captured by macrophages for presentation to T cells restricted to major histocompatibility complex class II. A conserved 36-kilodalton member of the tryptophan-aspartic acid repeat family of proteins was identified that was expressed in both stages of the parasite life cycle. A 24-kilodalton portion of this antigen protected susceptible mice when administered as a vaccine with interleukin-12 before infection.
B cell memory to thymus‐independent antigens type 1 and type 2: the role of lipopolysaccharide in B memory induction (1988)

Several studies have indicated that thymus-independent (TI) antigens, unlike their thymus-dependent (TD) counterparts, are poor at generating memory antibody responses (Immunol. Today 1981. 3:217). In contrast to this view, the present report shows that the TI type 1 (TI-1) antigen, 2,4,6-trinitrophenyl-lipopolysaccharide (TNP-LPS), elicits good secondary responses in rats. These secondary antibody responses are not only greater in magnitude than the primary responses, but display a different pattern of Ig classes with more IgG and IgA antibodies produced. In transfer experiments between congenic strains of rats which differ in their kappa light chain Ig allotype, it is shown that this memory is attributable to persistent B cell clones. The TI-2 antigen, 2,4-dinitrophenyl-hydroxyethyl starch (DNP-HES), given alone did not elicit B cell memory. However, when DNP-HES is presented to the immune system in association with LPS, the pattern of the anti-DNP response is similar to that elicited by TNP-LPS. The capacity to generate TI memory is associated with the appearance of hapten-specific B cells in the marginal zones of the spleen. Hapten-binding cells were induced in the marginal zones following immunization with TNP-LPS, but not by DNP-HES. However, concurrent immunization with DNP-HES and LPS which were not covalently linked was found to induce DNP-binding cells in the marginal zone. There is complete correlation between the appearance of hapten-binding memory B cells in the marginal zone and the capacity of these antigens to induce secondary responses.
Outer-membrane protein and lipopolysaccharide serotyping of Neisseria meningitidis by inhibition of a solid-phase radioimmunoassay (1977)

A new procedure involving inhibition of a solid-phase radioimmunoassay was developed for specific determination of the outer-membrane protein and the lipopolysaccharide (LPS) serotypes of meningococci. Antigen was allowed to bind to the wells of a polyvinyl microtiter plate and then reacted with a limiting amount of homologous antibody which had been preincubated with buffer or a standard concentration of inhibiting antigen. The amount of antibody bound per well was quantitated by incubation with excess 125I-labeled goat anti-rabbit immunoglobulin. Typing sera for detecting eight LPS antigens and 18 protein antigens were made in rabbits by use of both the group C and group B bactericidal serotyping strains. Reactions between unabsorbed sera and purified LPS were inhibited in the LPS typing system, whereas reactions between absorbed sera and outer-membrane complex were inhibited in the protein typing system. Outer-membrane complex was used as the inhibiting antigen in both cases. Approximately 97% of the 80 group B and C strains tested were LPS typable, and 80% were protein typable. Of 51 group A strains tested, however, only 22% were LPS typable and 14% were protein typable. Several nonreciprocal correlations between the occurrence of particular LPS and protein serotype antigens on the same strain were observed, but in general the protein and LPS serotype antigens appeared to occur independently.
Assessing ADHD and Comorbid Disorders in Children: The Child Behavior Checklist and the Devereux Scales of Mental Disorders (2000)

Evaluated discriminant validity and clinical utility of selected subscales of the Devereux Scales of Mental Disorders (DSMD; Naglieri, LeBuffe, & Pfeiffer, 1994) and the Child Behavior Checklist (CBCL; Achenbach, 1991a) in 228 children referred to a clinic for the evaluation and treatment of attention deficit hyperactivity disorder (ADHD). The DSMD is a multiaxial behavior rating scale that measures symptomatology for a broad range of child psychopathology as described in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-R-III] and 4th ed. [DSM-IV]; American Psychiatric Association, 1987, 1994). Discriminant function analyses as well as sensitivity, specificity, and predictive power analyses were computed to evaluate the discriminant validity and clinical utility of selected DSMD and CBCL subscales for assessing ADHD, oppositional defiant disorder (ODD), and anxiety disorders. Results indicated that the DSMD compared very favorably with the CBCL in the ability to discriminate between children with ADHD and those without ADHD and between children with comorbid ODD and anxiety disorders and children who did not meet criteria for these disorders. The DSMD Attention subscale may be somewhat better at ruling in ADHD combined subtype (ADHD-C) and ADHD inattentive subtype (ADHD-I) than the CBCL Attention Problems subscale, but the CBCL Attention Problems subscale may have slightly better utility than the DSMD Attention subscale in ruling out these subtypes. Both the CBCL and DSMD were more useful for ruling out than for ruling in ODD and anxiety disorders.
Immunomagnetic bead isolation of megakaryocytes from guinea‐pig bone marrow: effect of recombinant interleukin‐6 on size, ploidy and cytoplasmic fragmentation (1991)

Guinea-pig bone marrow megakaryocytes were isolated using an antibody to platelet glycoprotein Ib and a second antibody conjugated to magnetic beads. The procedure yielded an average of 644,800 megakaryocytes from two guinea-pigs with an average viability of 83%. All of the platelet glycoprotein Ib positive cells also expressed the platelet glycoprotein IIb-IIIa complex. The size and ploidy of megakaryocytes isolated by this technique were analysed in the presence of 10 ng/ml of interleukin-6 (IL-6). Without IL-6 megakaryocyte size increased significantly after 24 h, but an even larger increase in size occurred in the presence of IL-6. The modal ploidy class was 16N with an average of 19% 2N, 2.6% 4N, 16.4% 8N, 50.8% 16N and 11.1% 32N cells as determined by flow cytometry. Measurements made by microspectrophotometry were in close agreement. After 24 h incubation there was a significant rise in the percentage of 2N and 32N cells. The ploidy distribution after 24 h with IL-6 was the same as the control. Megakaryocytes cultured in the absence of serum on collagen gels did not form pseudopods and fragment, as occurs with serum (Leven et al, 1987). Addition of IL-6 to the serum-free cultures caused megakaryocytes to form extensive proplatelet extensions. We conclude that large numbers of pure guinea-pig bone marrow megakaryocytes can be isolated by immunomagnetic bead selection, including low ploidy immature megakaryocytes. Spontaneous maturation occurred as evidenced by the increase in megakaryocyte size and ploidy. IL-6 altered megakaryocyte size and morphology but not ploidy, indicating that these different characteristics of megakaryocytes may be regulated separately.
Smooth and time-optimal trajectory planning for industrial manipulators along specified paths (2000)

This article presents a method for determining smooth and time-optimal path constrained trajectories for robotic manipulators and investigates the performance of these trajectories both through simulations and experiments. The desired smoothness of the trajectory is imposed through limits on the torque rates. The third derivative of the path parameter with respect to time, the pseudo-jerk, is the controlled input. The limits on the actuator torques translate into state-dependent limits on the pseudo-acceleration. The time-optimal control objective is cast as an optimization problem by using cubic splines to parametrize the state space trajectory. The optimization problem is solved using the flexible tolerance method. The experimental results presented show that the planned smooth trajectories provide superior feasible time-optimal motion. © 2000 John Wiley & Sons, Inc.
Efficacy of an Inactivated Feline Leukemia Virus Vaccine (1996)

An inactivated whole-virus FeLV vaccine, developed from a molecularly cloned FeLV isolate (FeLV-61E-A), was assessed for its ability to protect cats against homologous and heterologous virulent viral challenge. The fractions of cats that resisted the induction of persistent viremia after FeLV challenge were as follows: FeLV-61E-A vaccine, 95%; adjuvant controls, 26%; and established commercial control FeLV vaccine, 35%. The prechallenge mean neutralizing antibody titers for each group were as follows: FeLV-61E-A vaccine, 1:43; adjuvant controls, < 1:8; and commercial control FeLV vaccine, 1:12. The prototype FeLV-61E-A vaccine was developed commercially for immunization of pet cats by substitution of a proprietary adjuvant and development of stable, high antigen production cell lines. This vaccine (Fel-O-Vax) has been studied extensively, alone and in multivalent combination with other feline virus vaccines, in seven efficacy trials involving a total of 150 immunized cats. These studies yielded an FeLV-resistant fraction of 87% in vaccinated cats as compared with 8% in adjuvant controls. The duration of immunity induced by an FeLV-61E-A commercial vaccine (Fel-O-Vax-LvK IV) was also assessed. One year after vaccination, 100% of challenged vaccinated cats and none of challenged controls resisted induction of persistent viremia. The results of these studies demonstrate that an inactivated FeLV vaccine prepared from a molecularly cloned subgroup A FeLV produces a high level of protective immunity against heterologous and homologous FeLV infection. This vaccine-induced immunity is durable for at least 1 year without intervening booster immunization or exposure to virus.
Continuous privacy preserving publishing of data streams (2009)

Recently, privacy preserving data publishing has received a lot of attention in both research and applications. Most of the previous studies, however, focus on static data sets. In this paper, we study an emerging problem of continuous privacy preserving publishing of data streams which cannot be solved by any straightforward extensions of the existing privacy preserving publishing methods on static data. To tackle the problem, we develop a novel approach which considers both the distribution of the data entries to be published and the statistical distribution of the data stream. An extensive performance study using both real data sets and synthetic data sets verifies the effectiveness and the efficiency of our methods.
A single ascending‐dose study of muscle regulator ace‐031 in healthy volunteers (2012)

Single-dose ACE-031 treatment was generally well-tolerated and resulted in increases in muscle mass in healthy postmenopausal women.
Bioengineered Skin Allografts: A New Method To Prevent Humoral Response (2011)

We previously reported that a bioengineered interface consisting of a nano-barrier membrane (NB-LVF4) used as an artificial interface between skin allografts and wound surfaces significantly prolonged graft survival without immunosuppression. We now evaluated whether NB-LVF4 could serve as a targeted drug delivery system to further improve outcomes. Fibroblast growth factor-1 (FGF-1) was selected for its known function as a wound hormone. Full-thickness 8-mm skin grafts were cross-transplanted between out-bred mice. Controls were transplanted without treatment. In test groups, the NB-LVF4, with or without FGF-1, was applied to both basolateral skin and wound surfaces with polymerization resulting in a tridimensional transparent membrane. The mice were evaluated for T-cell activation and development of donor-specific antibody. Rejection occurred in controls by 7 days. NB-LVF4 treatment, with or without FGF-1, was found to significantly prolong allograft survival (27 and 28 days, respectively [p < 0.05]). Untreated controls stimulated 10-fold shift in the number of circulating CD4+ cells while test groups exhibited substantially reduced shifts in CD4+ cells. The group treated with FGF-1 did not develop donor-specific antibody. Treatment with the NB-LVF4 membrane delays the onset of allograft rejection in the absence of systemic immunosuppression. FGF-1 appears to prevent the development of a humoral response by preventing B cell activation.
Quantitation of Neutral Lipid Mixtures Using High Performance Liquid Chromatography with Light Scattering Detection (1997)

Abstract A high performance liquid chromatographic (HPLC) method was developed for quantifying reaction mixtures obtained from the lipase-catalyzed transesterification of fats and oils. The reaction mixtures of interest were composed of neutral lipid classes that include alkyl esters, free fatty acids, triglycerides, 1,2- and 1,3-diglycerides, and 1 (2)-monoglycerides. The method, a modification of a literature procedure, uses a binary mobile phase of hexane (A) and methyl-t-butyl ether (B) each modified with acetic acid (0.4%) and a gradient elution profile that reduced analyses' times by 25%. Lipid classes were measured by use of an evaporative light scattering detector (ELSD). Precision of injection and linearity of response of the ELSD over the range of sample amounts of interest were established for the lipid classes measured by use of standards. The method was applied to the compositional analysis of prospective biofuel alkyl esters prepared from fats, oils, and recycled greases.
The Human Homologue of Bub3 Is Required for Kinetochore Localization of Bub1 and a Mad3/Bub1-related Protein Kinase (1998)

A feedback control mechanism, or cell cycle checkpoint, delays the onset of anaphase until all the chromosomes are correctly aligned on the mitotic spindle. Previously, we showed that the murine homologue of Bub1 is not only required for checkpoint response to spindle damage, but also restrains progression through a normal mitosis (Taylor, S.S., and F. McKeon. 1997. Cell. 89:727-735). Here, we describe the identification of a human homologue of Bub3, a 37-kD protein with four WD repeats. Like Bub1, Bub3 localizes to kinetochores before chromosome alignment. In addition, Bub3 and Bub1 interact in mammalian cells. Deletion mapping was used to identify the domain of Bub1 required for binding Bub3. Significantly, this same domain is required for kinetochore localization of Bub1, suggesting that the role of Bub3 is to localize Bub1 to the kinetochore, thereby activating the checkpoint in response to unattached kinetochores. The identification of a human Mad3/Bub1-related protein kinase, hBubR1, which can also bind Bub3 in mammalian cells, is described. Ectopically expressed hBubR1 also localizes to kinetochores during prometaphase, but only when hBub3 is overexpressed. We discuss the implications of the common interaction between Bub1 and hBubR1 with hBub3 for checkpoint control.
Steroid Hormones in the Development of Postpartum Depression (2014)

Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period around spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chromatography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already the changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that changes in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to postpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period.