gebhart/patrepeval huggingface dataset:
Effect of ultrasonic (cavitation) treatment of the melt on the microstructure evolution during solidification of aluminum alloy ingots (2002)

Abstract The development of methods for the ultimate cast structure refinement is among major tasks of light metals metallurgy. The production of billets with the ultimately refined grain structure and, therefore, the improved plasticity extends the capabilities of continuous casting and hot deformation, allowing the production of defect-free billets and deformed semi-products. Moreover, the fine structure of a billet is inherited by the deformed metal and improves its resource characteristics. This paper summarizes the results of extended research performed in VILS during last 30 years, in particular in the field of the formation of the ultimately refined (non-dendritic) grain structure during casting light alloys with the aid of ultrasonic (cavitation) melt treatment.
Antitumor Activity of Lenvatinib (E7080): An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models (2014)

Inhibition of tumor angiogenesis by blockading the vascular endothelial growth factor (VEGF) signaling pathway is a promising therapeutic strategy for thyroid cancer. Lenvatinib mesilate (lenvatinib) is a potent inhibitor of VEGF receptors (VEGFR1-3) and other prooncogenic and prooncogenic receptor tyrosine kinases, including fibroblast growth factor receptors (FGFR1-4), platelet derived growth factor receptor α (PDGFRα), KIT, and RET. We examined the antitumor activity of lenvatinib against human thyroid cancer xenograft models in nude mice. Orally administered lenvatinib showed significant antitumor activity in 5 differentiated thyroid cancer (DTC), 5 anaplastic thyroid cancer (ATC), and 1 medullary thyroid cancer (MTC) xenograft models. Lenvatinib also showed antiangiogenesis activity against 5 DTC and 5 ATC xenografts, while lenvatinib showed in vitro antiproliferative activity against only 2 of 11 thyroid cancer cell lines: that is, RO82-W-1 and TT cells. Western blot analysis showed that cultured RO82-W-1 cells overexpressed FGFR1 and that lenvatinib inhibited the phosphorylation of FGFR1 and its downstream effector FRS2. Lenvatinib also inhibited the phosphorylation of RET with the activated mutation C634W in TT cells. These data demonstrate that lenvatinib provides antitumor activity mainly via angiogenesis inhibition but also inhibits FGFR and RET signaling pathway in preclinical human thyroid cancer models.
Isolation and mapping of a human gene (RPD3L1) that is homologous to <i>RPD3</i>, a transcription factor in <i>Saccharomyces cerevisia</i><i>e</i> (1996)

We have isolated a novel human gene RPD3L1, that is highly homologous to a transcription factor in Saccharomyces cerevisiae, RPD3 (reduced potassium dependency 3), from a human fetal lung cDNA library. The cDNA clone, hRPD3, consists of 2,100 nucleotides that contain an open reading frame of 1446 nucleotides encoding 482 amino acids. It shares 62% identity in nucleotide sequence and 52% identity in amino acid sequence to RPD3. This gene is expressed at various levels in all tissues examined. Furthermore, we were able to map it to chromosome band 1p34.1 by FISH.
Congestive Heart Failure: Potential Role of Arginine Vasopressin Antagonists in the Therapy of Heart Failure (2002)

Neurohormonal imbalances clearly contribute to the pathophysiology of chronic congestive heart failure. Agents that interfere with the generation or effects of angiotensin II and aldosterone, or which block the effects of excess sympathetic drive, all favorably affect mortality. Arginine vasopressin, through its V(1A) and V(2) receptor-mediated effects, could theoretically also contribute to progression of left ventricular dysfunction and heart failure by aggravating systolic and diastolic wall stress, and by directly stimulating myocardial hypertrophy. Arginine vasopressin levels are increased in congestive heart failure patients; acutely, both V(1A) and V(2) antagonists produce beneficial hemodynamic responses in both clinical and experimental congestive heart failure. Experimental studies also indicate beneficial effects of V(1A) and V(2) antagonists (alone or in combination) on hemodynamics and possibly ventricular remodeling after myocardial injury. Currently, there are no long-term studies of any type of arginine vasopressin antagonist in human heart failure, but both the theoretical rationale and preclinical data would appear to justify such efforts.
Silicon Nanotube Battery Anodes (2009)

We present Si nanotubes prepared by reductive decomposition of a silicon precursor in an alumina template and etching. These nanotubes show impressive results, which shows very high reversible charge capacity of 3247 mA h/g with Coulombic efficiency of 89%, and also demonstrate superior capacity retention even at 5C rate (=15 A/g). Furthermore, the capacity in a Li-ion full cell consisting of a cathode of LiCoO2 and anode of Si nanotubes demonstrates a 10 times higher capacity than commercially available graphite even after 200 cycles.
Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice (1997)

Platelet-derived growth factor (PDGF)-B-deficient mouse embryos were found to lack microvascular pericytes, which normally form part of the capillary wall, and they developed numerous capillary microaneurysms that ruptured at late gestation. Endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells. Pericytes may contribute to the mechanical stability of the capillary wall. Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts.
Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. (2020)

The protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) plays a critical role in acute leukemias with translocations of the MLL1 gene or with mutations in the nucleophosmin 1 (NPM1) gene. As a step toward clinical translation of menin-MLL1 inhibitors, we report development of MI-3454, a highly potent and orally bioavailable inhibitor of the menin-MLL1 interaction. MI-3454 profoundly inhibited proliferation and induced differentiation in acute leukemia cells and primary patient samples with MLL1 translocations or NPM1 mutations. When applied as a single agent, MI-3454 induced complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia, including patient-derived xenograft models, through downregulation of key genes involved in leukemogenesis. We also identified MEIS1 as a potential pharmacodynamic biomarker of treatment response with MI-3454 in leukemia, and demonstrated that this compound is well tolerated and did not impair normal hematopoiesis in mice. Overall, this study demonstrates, for the first time to our knowledge, profound activity of the menin-MLL1 inhibitor as a single agent in clinically relevant PDX models of leukemia. These data provide a strong rationale for clinical translation of MI-3454 or its analogs for leukemia patients with MLL1 rearrangements or NPM1 mutations.
Functionalized Poly(α-hydroxy acid)s via Ring-Opening Polymerization:  Toward Hydrophilic Polyesters with Pendant Hydroxyl Groups (2006)

Two functionalized dilactones with protected hydroxyl groups, benzyloxymethyl methyl glycolide (4a) and benzyloxymethyl glycolide (4b), were synthesized and converted to the corresponding polyesters by ring-opening polymerization in the melt (at 110 °C using benzyl alcohol and SnOct2 as initiator and catalyst, respectively, and at 130 °C using SnOct2 as catalyst or in solution at 35 °C using ethylzinc phenolate and 2-propanol as catalyst and initiator, respectively). The obtained polymers were amorphous, with a glass transition temperature (Tg) between 15 and 45 °C. 13C NMR analysis showed that poly(4b) was perfectly alternating, owing to a regioselective ring opening, whereas poly(4a) had a random distribution of methyl and benzyloxymethyl side groups. Both 4a and 4b could be copolymerized with l-lactide. Copolymers of l-lactide with 4b showed crystallinity at 75% lactide content, whereas copolymers with 4a were amorphous at the same lactide content. Monomer 4b apparently reacts faster than lactide, resulting in composition drift and finally yielding a polymer rich in lactide and consequently in lactide blocks that are large enough to crystallize. Block copolymers were synthesized by sequential polymerization of l-lactide and 4a using ethylzinc phenolate as catalyst. Deprotection of the benzyloxymethyl groups of poly(4a) and poly(4b) gave the corresponding hydroxylated polyesters, which were amorphous and semicrystalline, respectively, according to DSC analysis.
Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Carcinoma (2001)

Flavopiridol administered as a single agent for 72 hours every 14 days is inactive in the treatment of gastric cancer. The drug also induced an unexpected higher incidence of vascular thrombosis and fatigue than was anticipated from the phase I trials. Future development of flavopiridol will depend on other doses and schedules in combination with chemotherapy.
Mechanisms of Tumor Regression and Resistance to Estrogen Deprivation and Fulvestrant in a Model of Estrogen Receptor–Positive, HER-2/neu-Positive Breast Cancer (2006)

HER-2/neu in breast cancer is associated with tamoxifen resistance, but little data exist on its interaction with estrogen deprivation or fulvestrant. Here, we used an in vivo xenograft model of estrogen receptor (ER)-positive breast cancer with HER-2/neu overexpression (MCF7/HER-2/neu-18) to investigate mechanisms of growth inhibition and treatment resistance. MCF7/HER-2/neu-18 tumors were growth inhibited by estrogen deprivation and with fulvestrant, but resistance developed in 2 to 3 months. Inhibited tumors had reductions in ER, insulin-like growth factor-I receptor (IGF-IR), phosphorylated HER-2/neu (p-HER-2/neu), and phosphorylated p42/44 mitogen-activated protein kinase (p-MAPK). p27 was increased especially in tumors sensitive to estrogen deprivation. Tumors with acquired resistance to these therapies had complete loss of ER, increased p-HER-2/neu, increased p-MAPK, and reduced p27. In contrast, IGF-IR and phosphorylated AKT (p-AKT) levels were markedly reduced in these resistant tumors. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib, which can block EGFR/HER-2/neu signaling, significantly delayed the emergence of resistance to both estrogen deprivation and fulvestrant. Levels of p-MAPK and p-AKT decreased with gefitinib, whereas high ER levels were restored. Eventually, however, tumors progressed in mice treated with gefitinib combined with estrogen deprivation or fulvestrant accompanied again by loss of ER and IGF-IR, increased p-HER-2/neu, high p-MAPK, and now increased p-AKT. Thus, estrogen deprivation and fulvestrant can effectively inhibit HER-2/neu-overexpressing tumors but resistance develops quickly. EGFR/HER-2/neu inhibitors can delay resistance, but reactivation of HER-2/neu and signaling through AKT leads to tumor regrowth. Combining endocrine therapy with EGFR/HER-2/neu inhibitors should be tested in clinical breast cancer, but a more complete blockade of EGFR/HER-2/neu may be optimal.
1.5-D high intensity focused ultrasound array for non-invasive prostate cancer surgery (2002)

The aim of this study is to demonstrate the feasibility of a new spherically curved 1.5-D phased array for the treatment of localized prostatic cancer. The device is designed to conform to the Ablatherm machine (EDAP-Technomed, France), a commercially available machine in which high intensity focused ultrasound (HIFU) treatment for prostate cancer is administered transrectally. It uses high intensity electronically focused ultrasound to steer a beam along two axes, allowing enough depth to be reached to treat large prostates and eliminating two degrees of mechanical movement. Through computer simulation, it was determined that a curved 1.5-D configuration offered the optimal design. Two configurations were then proposed, and their ability to steer a beam within a target volume centered on the geometric focus of the transducer was simulated. An eight-element prototype was constructed to test the piezo-composite material and its electro-acoustical efficiency. Then, an array was constructed, and a multi-channel amplifier and control system were added, to permit remote operation. Acoustical and electrical measurements were made to verify performance. Finally, the 1.5-D array was tested in vitro on samples of pig liver to confirm the ability to induce lesions.
Get the Message Out: Cyclic-Di-GMP Regulates Multiple Levels of Flagellum-Based Motility (2007)

Flagella are complex organelles whose synthesis depends upon approximately 50 gene products.Not surprisingly, multiple mechanisms control and direct flagellar biogenesis (reviewed in references 1, 15, and 55).Perhaps best understood is the control exerted at the level of transcription: hierarchies exist, such that the flagellar structural proteins are synthesized only under proper conditions and at the time each is needed for assembly.Many bacteria also possess posttranscriptional mechanisms that control translation or protein stability.Assembly itself also occurs in a highly ordered fashion, with the insertion of one component building on the insertion of a previous subunit.In the best-characterized bacteria, flagellar biogenesis begins with the insertion of an inner membrane protein called FliF (Fig. 1).Building on the assembled FliF subunits are proteins that comprise the flagellar type III secretory (TTS) apparatus.This device exports the protein subunits required to build the basal body, which includes both a cytoplasmic switching device and a complex of rod and ring proteins that spans the two membranes of the gram-negative bacterium.The completed basal body provides a narrow channel through which the more external components exit the cell for assembly.These external components include the hook (a flexible linker comprised of over 100 identical subunits) and the filament (a semirigid propeller built from thousands of flagellin subunits).Once assembled, the flagellum rotates, a process powered by the proton (or sodium) motive force via motor proteins localized in the cytoplasmic membrane in close proximity to the switching device.The direction of rotation is dictated by the switching device, which interfaces with a signaling pathway that delivers information about the cell's physicochemical environment.Chemotaxis, the resulting behavior, permits cells to migrate toward favorable environments.Finally, some bacteria eject their fully functional flagellum in coordination with the cell cycle.In recent years, researchers have discovered a new layer of regulation on top of the already sophisticated control of flagellar biogenesis and function.This layer depends on bis-(3Ј,5Ј)cyclic diguanylic acid (also known as cyclic diguanylate, or c-di-GMP), a novel second messenger that apparently is unique to bacteria.This newly appreciated second messenger
Domain swap chimeras to study the binding of IgG by FcγRI, the high affinity receptor for IgG (1996)

Conference Article| February 01 1996 Domain swap chimeras to study the binding of IgG by FcγRI, the high affinity receptor for IgG Patrick T. Harrison; Patrick T. Harrison 1Division of Biochemistry and Molecular Biology and Department of Medicine and Therapeutics, University of Glasgow, Glasgow G12 8QQ, U.K. Search for other works by this author on: This Site PubMed Google Scholar Janet M. Allen Janet M. Allen 1Division of Biochemistry and Molecular Biology and Department of Medicine and Therapeutics, University of Glasgow, Glasgow G12 8QQ, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1996) 24 (1): 144S. https://doi.org/10.1042/bst024144s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Patrick T. Harrison, Janet M. Allen; Domain swap chimeras to study the binding of IgG by FcγRI, the high affinity receptor for IgG. Biochem Soc Trans 1 February 1996; 24 (1): 144S. doi: https://doi.org/10.1042/bst024144s Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1996 Biochemical Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.
Central β-adrenergic modulation of cognitive flexibility (2002)

Situational stressors and anxiety impede performance on creativity tests requiring cognitive flexibility. Preliminary research revealed better performance on a task requiring cognitive flexibility, the anagram task, after propranolol (beta-adrenergic antagonist) than after ephedrine (beta-adrenergic agonist). However, propranolol and ephedrine have both peripheral and central beta-adrenergic effects. In order to determine whether noradrenergic modulation of cognitive flexibility is a centrally or peripherally mediated phenomenon, we compared the effects of propranolol (peripheral and central beta-blocker), nadolol (peripheral beta-blocker), and placebo on anagram task performance. Solution latency scores for each subject were compared across the drug conditions. Anagram solution latency scores after propranolol were significantly lower than after nadolol. This suggests a centrally mediated modulatory influence of the noradrenergic system on cognitive flexibility.
Identification of two murine loci homologous to the v-cbl oncogene (1989)

The virally transduced oncogene v-cbl transforms fibroblasts in vitro and induces early B-cell-lineage lymphomas in vivo. A series of probes derived from a molecular clone of v-cbl were used to map related sequences in the mouse genome. Analyses of Chinese hamster x mouse somatic-cell hybrids showed that two related genes, cbl-1 and cbl-2, were located on chromosomes 6 and 9, respectively. Restriction enzyme studies of DNA from hybrid cells containing either chromosome 6 or 9 suggested that cbl-1 resembles v-cbl and may be a processed gene, whereas cbl-2 has a complex genomic structure. Analyses of Mus domesticus/M. spretus interspecific backcross mice showed that Cbl-1 maps between the immunoglobulin kappa light chain and T-cell receptor beta chain loci and that Cbl-2 is tightly linked to Thy-1.
BACE1 Structure and Function in Health and Alzheimers Disease (2008)

Amyloid plaques, hallmark neuropathological lesions in Alzheimer's disease (AD) brain, are composed of the beta-amyloid peptide (Abeta). Much evidence suggests that Abeta is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. Given the strong correlation between Abeta and AD, therapeutic strategies to lower cerebral Abeta levels should prove beneficial for AD treatment. Abeta is derived from amyloid precursor protein (APP) via cleavage by two proteases, beta- and gamma-secretase. The beta-secretase has been identified as a novel aspartic protease named BACE1 (beta-site APP Cleaving Enzyme 1) that initiates Abeta formation. Importantly, BACE1 appears to be dysregulated in AD. As the rate-limiting enzyme in Abeta generation, BACE1, in principle, is an excellent therapeutic target for strategies to reduce the production of Abeta in AD. While BACE1 knockout (BACE1-/-) mice have been instrumental in validating BACE1 as the authentic beta-secretase in vivo, data indicates that complete abolishment of BACE1 may be associated with specific behavioral and physiological alterations. Recently a number of non-APP BACE1 substrates have been identified. It is plausible that failure to process certain BACE1 substrates may underlie some of the reported abnormalities in the BACE1-/- mice. Here we review the basic biology of BACE1, focusing on the regulation, structure and function of this enzyme. We pay special attention to the putative function of BACE1 during normal conditions and discuss in detail the relationship that exists between key risk factors for AD and the pathogenic alterations in BACE1 that are observed in the diseased state.
Amyloid fibril formation by pulmonary surfactant protein C (1999)

Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric alpha-helix into beta-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.
Basic fibroblast growth factor enhances bone‐graft incorporation: Dose and time dependence in rats (1996)

In a previous study, we found that basic fibroblast growth factor could stimulate bone-graft incorporation. In the present study, the effects of different doses and implantation times were further studied, using the bone conduction chamber, in rats. Inside the chamber, the graft is isolated from the surrounding tissues except at one end, where small openings embedded in host bone allow ingrowth of tissue. The distance that new tissues had reached from the openings into the graft was measured on histological slides. Bone grafts were obtained from the proximal tibiae of donor rats, frozen at -70 degrees C, and lipid-extracted. Before implantation, they were soaked overnight in a hyaluronate gel with or without basic fibroblast growth factor and then were fitted into the chambers, which were implanted in the proximal tibiae of recipient rats. In a dose-response experiment, grafts containing 0.3, 8, 40, 200, or 1,000 ng of basic fibroblast growth factor were compared with grafts treated with carrier gel only, after an implantation time of 6 weeks. Fibrous tissue always penetrated the grafts further than the ingrown bone; the distance that it reached from the ingrowth openings (total ingrowth distance) was increased by all of the doses except 0.3 ng per implant. The distance of bone ingrowth was increased by 8, 40, and 200 ng. The increased total ingrowth with 1,000 ng was due to an increased amount of fibrous tissue ahead of the bone, whereas with the lower doses the increase was due to more bone. Thus, the dose had an effect on the type of ingrown tissue found in the graft. In a time-effect study, grafts treated with 40 ng of basic fibroblast growth factor had a higher uptake of [99mTc]MDP at 2 and 4 weeks and an increased bone ingrowth distance at 10 weeks. The radioactivity from [125I]basic fibroblast growth factor declined with a half-life of 17 hours. The results suggest that basic fibroblast growth factor may be beneficial for the incorporation of contained bone grafts; studies using more clinically relevant models are required.