gebhart/patrepeval huggingface dataset:
Hemodynamic effects of cardiac cycle-specific increases in intrathoracic pressure (1986)

Changes in intrathoracic pressure (ITP) can influence cardiac performance by affecting ventricular loading conditions. Because both systemic venous return and factors determining left ventricular (LV) ejection may vary over the cardiac cycle, phasic increases in ITP may differentially affect preload or afterload if delivered at specific points within the cardiac cycle. We studied the hemodynamic effects of cardiac cycle-specific increases in ITP (pulses) delivered by a high-frequency jet ventilator in an acute closed-chested canine model (n = 11), using electromagnetic flow probes to measure biventricular stroke volume. Measurements were taken during a control condition after the induction of acute ventricular failure (AVF) by propranolol hydrochloride and volume infusion. ITP was independently varied without changing lung volume by the inflation of thoracoabdominal binders. Although synchronous pulses had minimal hemodynamic effects in unbound controls, binding pulses timed to occur in early diastole resulted in decreases in LV filling pressure and left ventricular stroke volume (SVlv) (P less than 0.05). In the AVF condition, pulses increased LV performance, evidenced by increases in SVlv (P less than 0.01), despite decreases in LV filling pressure (P less than 0.05). This effect is maximized by binding and by timing the pulses to occur in systole. We conclude that cardiac cycle-specific increases in ITP can significantly affect cardiac performance. These effects appear to be related to the ability of such timed pulses to selectively affect LV preload and afterload.
Transforming growth factor-beta selectively inhibits branching morphogenesis but not tubulogenesis (1997)

When cultured in type I collagen gels, two kidney-derived cell lines, Madin-Darby canine kidney (MDCK) cells and murine inner medullary collecting duct (mIMCD3) cells, from branching tubular structures in the presence of Swiss 3T3 conditioned medium, in which hepatocyte growth factor (HGF) is the major branching tubule inducing factor. However, upon incubation with transforming growth factor-beta (TGF-beta) in the presence of 3T3 conditioned medium, MDCK tubulogenesis and branching was markedly inhibited. In contrast, mIMCD3 cells, which are much less susceptible to growth and tubulogenesis inhibition by TGF-beta, formed long straight tubulelike structures in presence of TGF-beta, suggesting a dissociation between tubulogenesis and branching morphogenesis. Interestingly, those long tubules that did branch often superficially resembled the early branching ureteric bud in embryonic kidneys. Quantitation of branching events revealed a selective branch-inhibiting effect of TGF-beta on mIMCD3 cells at concentrations between 0.02 and 2 ng/ml. There was no qualitative or quantitative difference among TGF-beta 1, -beta 2, and -beta 3 on inhibition of branching events, suggesting existence of potentially redundant mechanisms for modulating branching morphogenesis. Concentrations of TGF-beta that resulted in long nonbranching tubules also altered the profile of extracellular matrix-degrading proteases and their inhibitors expressed by developing tubules. Ratios of urokinase type plasminogen activator (u-PA) to plasminogen activator inhibitor (PAI-l) and matrix metalloprotease (MMP)-1 to tissue inhibitor of metalloprotease (TIMP)-1 were both markedly decreased. In addition, apart from a direct effect on epithelial cell branching morphogenesis, TGF-beta downregulated the expression of HGF mRNA in Swiss 3T3 cells. Thus TGF-beta exerts at least three distinct effects relevant to tubulogenesis and branching morphogenesis inhibition of branching morphogenesis alone (mIMCD3 cells), inhibition of both tubulogenesis and branching morphogenesis (MDCK cells), and inhibition of the expression of growth factor which induce tubulogenesis and branching morphogenesis (3T3 cells). In the context of epithelial tissue development, which requires tightly regulated branching tubulogenesis of epithelial cells, the data suggest a model where branching patterns are regulated by a precise temporal and spatial balance between branching morphogens such as HGF and inhibitory morphogens such as members of the TGF-beta superfamily [e.g., TGF-beta isoforms, certain bone morphogenetic proteins].
Mutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia (2008)

Genotypes defined by the mutational status of NPM1, FLT3, CEBPA, and MLL are associated with the outcome of treatment for patients with cytogenetically normal AML.
HER2Status and Benefit from Adjuvant Trastuzumab in Breast Cancer (2008)

To the Editor: Trastuzumab, an antibody against the protein product of the human epidermal growth factor receptor type 2 (HER2) gene, improves progression-free survival and overall survival when added to chemotherapy in patients with metastatic breast cancer.1 Initial trials enrolled patients with tumors that had a staining intensity of 2+ or 3+ for HER2 on immunohistochemical analysis, but in subsequent studies, the benefit was limited to tumors with HER2 amplification as determined by fluorescence in situ hybridization (FISH). Trastuzumab also improves disease-free survival and overall survival in the adjuvant setting.2 On the basis of its mechanism of action, . . .
THE EFFICIENT MARKET HYPOTHESIS: A SURVEY (2000)

The views expressed are those of the authors and should not be attributed to the The efficient market hypothesis states that asset prices in financial markets should reflect all available information; as a consequence, prices should always be consistent with ‘fundamentals’. In this paper, we discuss the main ideas behind the efficient market hypothesis, and provide a guide as to which of its predictions seem to be borne out by empirical evidence, and which do not. In examining the empirical evidence, we concentrate on the stock and foreign exchange markets. The efficient market hypothesis is almost certainly the right place to start when thinking about asset price formation. The evidence suggests, however, that it cannot explain some important and worrying features of asset market behaviour. Most importantly for the wider goal of efficient resource allocation, financial market prices appear at times to be subject to substantial misalignments, which can
Interferon system in primary acute lymphocytic leukemia cells with or without deletions of the alpha-/beta-interferon genes (1992)

Various aspects of the interferon (IFN) system were studied in malignant cells from 37 unselected patients with acute lymphocytic leukemia (ALL). It was found that leukemic cells from two of 37 patients had a complete loss of alpha- and beta-IFN genes, whereas cells from four of 37 had lost one of the alpha-/beta-IFN alleles. In 25 cases, viable cells were also available for functional studies. Cell clones with loss of one of the alpha-/beta-IFN alleles produced low amounts of IFN after virus induction in vitro. Some clones with an apparently normal set of IFN genes were unable to produce detectable amounts of IFN. All clones studied were found to carry high-affinity alpha-IFN receptors. In clones carrying deletions of IFN genes, the cells were sensitive to IFN in vitro as measured by alpha-IFN-induced enhancement of 2′,5′-oligoadenylate synthetase (2′,5′-A synthetase). Cells from four patients with an apparently normal set of IFN genes were insensitive to this effect of IFN. We conclude that of the 17 patients in which IFN genes, IFN production, alpha-IFN receptors, and IFN-induced enhancement of 2′,5′-A synthetase were studied, nine (53%) showed some abnormality in their IFN system. This finding may add some support to the hypothesis that defects in the IFN system could be a step on the path to malignant transformation in ALL. Moreover, patients whose malignant cells carry IFN gene deletions or other defects in their IFN-producing capacity, but are still sensitive to exogenous IFN, could represent a subgroup of ALL with a greater likelihood of responding to IFN therapy.
PtM/C Catalyst Prepared Using Reverse Micelle Method for Oxygen Reduction Reaction in PEM Fuel Cells (2008)

Synthesis of carbon-supported PtM/C catalysts (M = Co, Cr, or Fe) using a new preparation technique, a reverse micelle method, is reported. The catalysts were characterized by different surface techniques: X-ray diffraction, scanning electron microscope, transmission electron microscope, and energy dispersive X-ray microanalysis. Surface characterization showed that Pt/M nanoparticles on catalysts were synthesized using the reverse micelle method. Pt/M nanoparticles were observed to be uniform spherical objects. The performance of the PtM/C catalysts was tested by the rotating disk electrode technique. A trend of catalytic activity for oxygen reduction reaction (ORR) was obtained: PtCo/C(T, 500) ∼ PtCo/C(S) > PtCr/C(S) > PtFe/C(S) ∼ Pt/C > PtFe/C(T, 500) ∼ PtCr/C(T, 500), showing that PtCo/C-type catalysts had a higher catalytic activity for ORR.
The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis (2011)

Myeloid-derived suppressor cells (MDSC) are important to the tumour microenvironment as they actively suppress the immune system and promote tumour progression and metastasis. These cells block T-cell activation in the tumour microenvironment, preventing anti-tumour immune activity. The ability of a treatment to alter the suppressive function of these cells and promote an immune response is essential to enhancing overall therapeutic efficacy. Interleukin-12 (IL-12) has the potential not only to promote anti-tumour immune responses but also to block the activity of cells capable of immune suppression. This paper identifies a novel role for IL-12 as a modulator of MDSC activity, with implications for IL-12 as a therapeutic agent. Treatment with IL-12 was found to alter the suppressive function of MDSC by fundamentally altering the cells. Interleukin-12-treated MDSC exhibited up-regulation of surface markers indicative of mature cells as well as decreases in nitric oxide synthase and interferon-γ mRNA both in vitro and in vivo. Treatment with IL-12 was also found to have significant therapeutic benefit by decreasing the percentage of MDSC in the tumour microenvironment and increasing the percentage of active CD8(+) T cells. Treatment with IL-12 resulted in an increase in overall survival accompanied by a reduction in metastasis. The findings in this paper identify IL-12 as a modulator of immune suppression with significant potential as a therapeutic agent for metastatic breast cancer.
GUI ripping: reverse engineering of graphical user interfaces for testing (2004)

Graphical user interfaces (GUIs) are important parts oftoday's software and their correct execution is required toensure the correctness of the overall software. A populartechnique to detect defects in GUIs is to test them by executingtest cases and checking the execution results. Testcases may either be created manually or generated automaticallyfrom a model of the GUI. While manual testingis unacceptably slow for many applications, our experiencewith testing has shown that creating a model that canbe used for automated test case generation is difficult.We describe a new approach to reverse engineer a modelrepresented as structures called a forest, event-flowgraphs and an integration tree directly from the executableGUI. We describe GUI Ripping, a dynamic process inwhich the software's is automatically traversed byopening all its windows and extracting all their widgets(GUI objects), properties, and values. The extracted informationis then verified by the test designer and used to automaticallygenerate test cases. We present algorithms for theripping process and describe their implementation in a toolsuite that operates on Java and Microsoft Windows' GUIs.We present results of case studies which show that ourapproach requires very little human intervention and is especiallyuseful for regression testing of software that is modifiedfrequently. We have successfully used the GUI Ripperin several large experiments and have made it availableas a downloadable tool.
Supercritical thermal decomposition of cellulose: experiments and modeling (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSupercritical thermal decomposition of cellulose: experiments and modelingMotonobu Goto, Oner Hortacsu, and Ben J. McCoyCite this: Ind. Eng. Chem. Res. 1990, 29, 7, 1091–1095Publication Date (Print):July 1, 1990Publication History Published online1 May 2002Published inissue 1 July 1990https://pubs.acs.org/doi/10.1021/ie00103a001https://doi.org/10.1021/ie00103a001research-articleACS PublicationsRequest reuse permissionsArticle Views149Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Characterization of Phosphopeptide Motifs Specific for the Src Homology 2 Domains of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3 (2003)

Signal transducers and activators of transcription (STAT) 1 and STAT3 are activated by overlapping but distinct sets of cytokines. STATs are recruited to the different cytokine receptors through their Src homology (SH) 2 domains that make highly specific interactions with phosphotyrosine-docking sites on the receptors. We used a degenerate phosphopeptide library synthesized on 35-microm TentaGel beads and fluorescence-activated bead sorting to determine the sequence specificity of the peptide-binding sites of the SH2 domains of STAT1 and STAT3. The large bead library allowed not only peptide sequencing of pools of beads but also of single beads. The method was validated through surface plasmon resonance measurements of the affinities of different peptides to the STAT SH2 domains. Furthermore, when selected peptides were attached to a truncated erythropoietin receptor and stably expressed in DA3 cells, activation of STAT1 or STAT3 could be achieved by stimulation with erythropoietin. The combined analysis of pool sequencing, the individual peptide sequences, and plasmon resonance measurements allowed the definition of SH2 domain binding motifs. STAT1 preferentially binds peptides with the motif phosphotyrosine-(aspartic acid/glutamic acid)-(proline/arginine)-(arginine/proline/glutamine), whereby a negatively charged amino acid at +1 excludes a proline at +2 and vice versa. STAT3 preferentially binds peptides with the motif phosphotyrosine-(basic or hydrophobic)-(proline or basic)-glutamine. For both STAT1 and STAT3, specific high affinity phosphopeptides were identified that can be used for the design of inhibitory molecules.
On Setting the First Dose in Man: Quantitating Biotherapeutic Drug‐Target Binding through Pharmacokinetic and Pharmacodynamic Models (2009)

Although the three (perhaps four) phases of clinical drug development are well known, it is relatively unappreciated that there are similar phases in pre-clinical development. These consist of 'Phase I' the initial, normally Research Discovery driven pharmacology; 'Phase II' non-good laboratory practice (GLP) dose range finding, followed by pivotal 'Phase III' GLP toxicology. Together with an array of in vitro experiments comparing species, these stages should enable an integrated safety assessment prior to entry into man, documenting to investigators and authorities evidence that the new pharmaceutic is unlikely to cause harm. Following the lessons learned from TeGenero TGN1412 and subsequent updates to regulatory guidelines, there are aspects peculiar to biotherapeutics, especially those that target key body systems, where calculations could be made for doses for human studies using pharmacokinetic and pharmacodynamic models. Two of these are exemplified in this paper. In the first, target-mediated drug disposition, where the binding of the drug to a cellular target quantitatively affects the pharmacokinetics, enables occupancy to be estimated without recourse to independent assays. In the second, assaying captured soluble target, as drug-target complexes, allows estimation of the concentration of the free ligand ensuring that in initial clinical studies, soluble targets are not overly suppressed. To support this methodology, it has been demonstrated using omalizumab, free and total IgE data that such analyses do predict the suppression of the free unbound ligand with reasonable accuracy. Overall, the objective of the process is to deliver a justification, through consideration of drug-target binding, of a safe starting and therapeutically relevant escalation doses for human studies.
Fluid and Electrolyte Problems of Tube-Fed Patients (1976)

KUBO, WINIFRED; GRANT, MARCIA; WALIKE, BARBARA; BERGSTROM, NANCY; WONG, HILDA; HANSON, ROBERT; PADILLA, GERALDINE Author Information
Neural Circuits Subserving the Retrieval and Maintenance of Abstract Rules (2003)

Behavior is often governed by abstract rules or instructions for behavior that can be abstracted from one context and applied to another. Prefrontal cortex (PFC) is thought to be important for representing rules, although the contributions of ventrolateral (VLPFC) and dorsolateral (DLPFC) regions remain under-specified. In the present study, event-related fMRI was used to examine abstract rule representation in humans. Prior to scanning, subjects learned to associate unfamiliar shapes and nonwords with particular rules. During each fMRI trial, presentation of one of these cues was followed by a delay and then by sample and probe stimuli. Match and non-match rules required subjects to indicate whether or not the sample and probe matched; go rules required subjects to make a response that was not contingent on the sample/probe relation. Left VLPFC, parietal cortex, and pre-SMA exhibited sensitivity to rule type during the cue and delay periods. Delay-period activation in these regions, but not DLPFC, was greater when subjects had to maintain response contingencies (match, non-match) relative to when the cue signaled a specific response (go). In contrast, left middle temporal cortex exhibited rule sensitivity during the cue but not delay period. These results support the hypothesis that VLPFC interacts with temporal cortex to retrieve semantic information associated with a cue and with parietal cortex to retrieve and maintain relevant response contingencies across delays. Future investigations of cross-regional interactions will enable full assessment of this account. Collectively, these results demonstrate that multiple, neurally separable processes are recruited during abstract rule representation.
Inhibiting the HSP90 chaperone slows cyst growth in a mouse model of autosomal dominant polycystic kidney disease (2013)

Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic syndrome with an incidence of 1:500 in the population, arising from inherited mutations in the genes for polycystic kidney disease 1 (PKD1) or polycystic kidney disease 2 (PKD2). Typical onset is in middle age, with gradual replacement of renal tissue with thousands of fluid-filled cysts, resulting in end-stage renal disease requiring dialysis or kidney transplantation. There currently are no approved therapies to slow or cure ADPKD. Mutations in the PKD1 and PKD2 genes abnormally activate multiple signaling proteins and pathways regulating cell proliferation, many of which we observe, through network construction, to be regulated by heat shock protein 90 (HSP90). Inhibiting HSP90 with a small molecule, STA-2842, induces the degradation of many ADPKD-relevant HSP90 client proteins in Pkd1(-/-) primary kidney cells and in vivo. Using a conditional Cre-mediated mouse model to inactivate Pkd1 in vivo, we find that weekly administration of STA-2842 over 10 wk significantly reduces initial formation of renal cysts and kidney growth and slows the progression of these phenotypes in mice with preexisting cysts. These improved disease phenotypes are accompanied by improved indicators of kidney function and reduced expression and activity of HSP90 clients and their effectors, with the degree of inhibition correlating with cystic expansion in individual animals. Pharmacokinetic analysis indicates that HSP90 is overexpressed and HSP90 inhibitors are selectively retained in cystic versus normal kidney tissue, analogous to the situation observed in solid tumors. These results provide an initial justification for evaluating HSP90 inhibitors as therapeutic agents for ADPKD.
CO2 laser annular thermokeratoplasty: A preliminary study (1992)

Since most techniques of refractive surgery currently in use or being developed have the potential for significant side effects, there is a need for investigating alternative procedures. We herein report on the use of a pulsed CO2 laser beam delivered through a pair of complementary axicons to produce a ring of stromal collagen contraction resulting in the flattening of the corneal apex of cadaver eyes. Irradiances of 29 W/cm2 and 23 W/cm2 were used for rings of 5.5 mm and 7.0 mm, respectively. The creation of a ring of 7.0 mm in diameter did not affect the corneal curvature significantly but when the diameter was reduced to 5.5 mm, substantial flattening proportional to the dose of radiation took place. In our system, it was possible to achieve up to 11.3 diopters of mean keratometry flattening (90 joules, 5.5 mm of diameter). In addition, a 1 mm posterior displacement of the corneal dome without histological evidence of closure of the iridocorneal angle was observed. Annular thermokeratoplasty (ATK) may minimize side effects encountered with other refractive procedures since it does not require ablation, incisions, or interaction with the central optical zone.
Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets (2011)

Our results revealed the phenotype and effector function of PD-1-expressing T helper cell subsets and indicate that PD-1 restrains the B cell-helping function of germinal center-localized T cells to prevent excessive antibody response.
Secretion of Neurotoxins by Mononuclear Phagocytes Infected with HIV-1 (1990)

Mononuclear phagocytes (microglia, macrophages, and macrophage-like giant cells) are the principal cellular targets for human immunodeficiency virus-1 (HIV-1) in the central nervous system (CNS). Since HIV-1 does not directly infect neurons, the causes for CNS dysfunction in acquired immunodeficiency syndrome (AIDS) remain uncertain. HIV-1-infected human monocytoid cells, but not infected human lymphoid cells, released toxic agents that destroy chick and rat neurons in culture. These neurotoxins were small, heat-stable, protease-resistant molecules that act by way of N-methyl-D-aspartate receptors. Macrophages and microglia infected with HIV-1 may produce neurologic disease through chronic secretion of neurotoxic factors.