gebhart/patrepeval huggingface dataset:
The Anti-Tumor Effects of SU11248, a Class III Receptor Tyrosine Kinase Inhibitor, Against a Variety of Human Hematological Malignancies. (2005)

Abstract We studied anti-tumor effects of the class III receptor tyrosine kinase inhibitor SU11248 against a wide variety of hematological malignancies including the following leukemias: acute myeloid (THP-1, U937, Kasumi-1, MV4-11), acute lymphoblastic (NALL-1, Jurkat, BALL-2, PALL-1, -2), blast crisis of chronic myeloid (KU812, Kcl-22, K562) and adult T-cell (MT-1, -2, -4), as well as, non-Hodgkin’s lymphoma (KS-1, Dauji, Akata) and multiple myeloma (U266). Thymidine-uptake studies showed that SU11248 was active against MV4-11 and Kasumi-1 cells which possessed activating mutations of the FLT-3 and the c-Kit gene, respectively, with IC50s of approximately 30 nM. In addition, SU11248 inhibited the proliferation of Bcr/Abl-expressing KU812, Kcl-22, K562, PALL-1, and -2 cells with IC50s ranging from 2 to 5 uM. SU11248 induced apoptosis of these cells via activation of caspase 3 as measured by Annexin V staining and caspase assay. SU11248 inhibited phosphorylation of c-Abl and its downstream effectors Akt and STAT5 in these cells. Interestingly, mTOR inhibitor rapamycin enhanced the ability of SU11248 to inhibit the proliferation of Bcr/Abl-expressing cells. For example, SU11248 (2 uM, 48 h) or rapamycin (100 nM, 48 h) alone inhibited the proliferation of KU812 cells by 47 ± 6 % or 8 ± 6 %, respectively. When both were combined, their proliferation was inhibited by approximately 90 %. Furthermore, SU11248 (10 nM to 1 uM, 48 h) inhibited the proliferation of freshly-isolated leukemia cells from individuals with AML (15 cases) as well as Ph-positive ALL (1 case), who relapsed after treatment with conventional chemotherapy with imatinib. Profound growth inhibition by SU11248 (IC50s &amp;lt;10 nM) occurred in leukemia cells (4 cases) having an in-frame tandem duplications within the juxtamembrane region of FLT3 gene. Furthermore, rapamycin potentiated the anti-proliferative effects of SU11248 in the freshly-isolated leukemia cells. Taken together, SU11248 may be useful for treatment of individuals with variety of leukemias and the combination of SU11248 and rapamycin represents a promising novel treatment strategy.
Using IIDs to estimate sound source direction (2002)

Poster. Sounds recorded using a binaural head are analysed to find the azimuthal direction of a sound source. Two techniques for inter-aural intensity difference (IID) estimation are compared. In both, signals were filtered into a number of wideband logarithmically spaced frequency bands. In method 1, an estimate of the IID in each frequency band was made every 20ms, and in method 2, estimates were made only when a cluster of onsets had been found. Onsets were detected using a biologically plausible spike-based technique. IID vectors were converted to directions using estimates of the impulse response of the binaural head. The onset-based technique provides better results, particularly in reverberant environments. 1
C–H and C–C Activation of n-Butane with Zirconium Hydrides Supported on SBA15 Containing N-Donor Ligands: [(≡SiNH−)(≡SiX−)ZrH2], [(≡SiNH−)(≡SiX−)2ZrH], and[(≡SiN═)(≡SiX−)ZrH] (X = −NH–, −O−). A DFT Study (2014)

Density functional theory (DFT) was used to elucidate the mechanism of n-butane hydrogenolysis (into propane, ethane, and methane) on well-defined zirconium hydrides supported on SBA15 coordinated to the surface via N-donor surface pincer ligands: [(≡SiNH−)(≡SiO−)ZrH2] (A), [(≡SiNH−)2ZrH2] (B), [(≡SiNH−)(≡SiO−)2ZrH] (C), [(≡SiNH−)2(≡SiO−)ZrH] (D), [(≡SiN═)(≡Si–O−)ZrH] (E), and [(≡SiN═)(≡SiNH−)ZrH] (F). The roles of these hydrides have been investigated in C–H/C–C bond activation and cleavage. The dihydride A linked via a chelating [N,O] surface ligand was found to be more active than B, linked to the chelating [N,N] surface ligand. Moreover, the dihydride zirconium complexes are also more active than their corresponding monohydrides C–F. The C–C cleavage step occurs preferentially via β-alkyl transfer, which is the rate-limiting step in the alkane hydrogenolysis. The energetics of the comparative pathways over the potential energy surface diagram (PES) reveals the hydrogenolysis of n-butane into propane and ethane.
Syndecan-1 expression in cancer of the uterine cervix: Association with lymph node metastasis (2002)

The development of carcinoma is associated with alterations in the expression of many cell adhesion molecules. Syndecan-1 is a cell surface proteoglycan that binds cells to the extracellular matrix and changes its expression following malignant transformation in some tumors. Our purpose was to examine the pattern of syndecan-1 expression in cancer of the uterine cervix and assess the clinicopathological significance of syndecan-1 expression. A total of 106 tissue specimens (6 normal, 19 cervical intraepithelial neoplasia (CIN) and 81 invasive cancer) were analyzed immunohistochemically. In addition, the corresponding expression of mRNA in tumor tissues was evaluated by reverse transcription-polymerase chain reaction (RT/PCR) in comparison with normal counterparts. Syndecan-1 was positive in normal squamous cells except the basal cell layer. The intensity of syndecan-1 staining was the strongest in normal epithelium, followed by CIN, and invasive squamous cell carcinoma. Syndecan-1 expression in cancer tissue tended to be higher in keratinizing type than non-keratinizing type and not found in adenocarcinoma. Syndecan-1 expression was markedly decreased at the mRNA level in invasive squamous cell carcinoma as compared with that of normal uterine cervix. Interestingy, there was an inverse correlation between the expression of syndecan-1 in the primary site and lymph node metastasis, although there was no significant correlation between syndecan-1 expression and the prognosis. The results of the present study suggest that syndecan-1 expression is associated with squamous tissues and plays a key role in the progression of the cancer of the uterine cervix especially in the metastatic process.
Phase I/II trial of HIV-1 hyperimmune globulin for the prevention of HIV-1 vertical transmission in Uganda (2002)

An HIV immune globulin product derived from HIV infected Ugandan donors is safe, well tolerated, and has pharmacokinetic properties consistent with other immunoglobulin products. Data suggest that a 400 mg/kg dose of HIVIGLOB would be the most appropriate dose for a subsequent efficacy trial of HIVIGLOB for the prevention of mother to child HIV transmission.
Comparison of mixed anion, InAsyP1−y and mixed cation, InxAl1−xAs metamorphic buffers grown by molecular beam epitaxy on (100) InP substrates (2004)

The structural, morphological, and defect properties of mixed anion, InAsyP1−y and mixed cation, InxAl1−xAs metamorphic step-graded buffers grown on InP substrates are investigated and compared. Two types of buffers were grown to span the identical range of lattice constants and lattice mismatch (∼1.1–1.2%) on (100) InP substrates by solid source molecular beam epitaxy. Symmetric relaxation of ∼90% in the two orthogonal 〈110〉 directions with minimal lattice tilt was observed for the terminal InAs0.4P0.6 and In0.7Al0.3As overlayers of each graded buffer type, indicating nearly equal numbers of α and β dislocations were formed during the relaxation process and that the relaxation is near equilibrium and hence insensitive to asymmetric dislocation kinetics. Atomic force microscopy reveals extremely ordered crosshatch morphology and very low root mean square (rms) roughness of ∼2.2 nm for the InAsP relaxed buffers compared to the InAlAs relaxed buffers (∼7.3 nm) at the same degree of lattice mismatch with respect to the InP substrates. Moreover, phase decomposition is observed for the InAlAs buffers, whereas InAsP buffers displayed ideal, step-graded buffer characteristics. The impact of the structural differences between the two buffer types on metamorphic devices was demonstrated by comparing identical 0.6 eV band gap lattice-mismatched In0.69Ga0.31As thermophotovoltaic (TPV) devices that were grown on these buffers. Clearly superior device performance was achieved on InAsyP1−y buffers, which is attributed primarily to the impact of layer roughness on the carrier recombination rates near the front window/emitter interface of the TPV devices.
Ocular Surface Discomfort and Demodex: Effect of Tea Tree Oil Eyelid Scrub in Demodex Blepharitis (2012)

The purpose of this study was to evaluate the relation between ocular discomfort and ocular Demodex infestation, and therapeutic effects of tea tree oil (TTO) in Demodex blepharitis patients. Three hundred and thirty-five patients with ocular discomfort were evaluated for ocular Demodex infestation and subjective symptoms with ocular surface discomfort index (OSDI) score. Among them, Demodex-infested patients were randomized to receive either eyelid scrubbing with TTO (TTO group,106 patients) or without TTO (Control group, 54 patients) for 1 month. Demodex were found in 84% of patients with ocular discomfort. The number of Demodex was significantly correlated with age (P = 0.04) and OSDI score (P = 0.024). After eyelid scrub treatment, Demodex count was reduced from 4.0 ± 2.5 to 3.2 ± 2.3 in the TTO group (P = 0.004) and from 4.3 ± 2.7 to 4.2 ± 2.5 in the control group (P = 0.27). Also, OSDI score was reduced from 34.5 ± 10.7 to 24.1 ± 11.9 in the TTO group (P = 0.001) and from 35.3 ± 11.6 to 27.5 ± 12.8 in the control group (P = 0.04). In conclusion, Demodex number showed a significant positive correlation with age and subjective ocular discomfort. The tea tree oil eyelid scrub treatment is effective for eliminating ocular Demodex and improving subjective ocular symptoms.
A new family of zero-current-switching variable frequency DC-DC converters (2002)

A new family of zero-current-switching variable-frequency DC-DC power converters is presented. It employs two unidirectional current switches, one diode, two small reactive components and a filter capacitor. Zero current turn-on and turn-off ensure low switching losses and smooth current waveforms result in low electromagnetic noise emission. The discontinuous operating mode and the variable switching frequency make the presented topology suitable for low-power applications or for high-power low-frequency applications where SCRs can be profitably used. Experimental results of a prototype confirm the theoretical expectations of the proposed solution.
Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9 (2016)

Conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates is an important disease-associated posttranslational modification, although few inhibitors of this process are known. Herein, we report the discovery of an allosteric small-molecule binding site on Ubc9, the sole SUMO E2 enzyme. An X-ray crystallographic screen was used to identify two distinct small-molecule fragments that bind to Ubc9 at a site distal to its catalytic cysteine. These fragments and related compounds inhibit SUMO conjugation in biochemical assays with potencies of 1.9-5.8 mm. Mechanistic and biophysical analyses, coupled with molecular dynamics simulations, point toward ligand-induced rigidification of Ubc9 as a mechanism of inhibition.
Design of Quantum Dot-Conjugated Lipids for Long-Term, High-Speed Tracking Experiments on Cell Surfaces (2008)

The current study reports the facile design of quantum dot (QD)-conjugated lipids and their application to high-speed tracking experiments on cell surfaces. CdSe/ZnS core/shell QDs with two types of hydrophilic coatings, 2-(2-aminoethoxy)ethanol (AEE) and a 60:40 molar mixture of 1,2-dipalmitoyl- sn-glycero-3-phosphocholine and 1,2-dipalmitoyl- sn-glycero-3-phosphoethanolamine- N-[methoxy(polyethylene glycol-2000], are conjugated to sulfhydryl lipids via maleimide reactive groups on the QD surface. Prior to lipid conjugation, the colloidal stability of both types of coated QDs in aqueous solution is confirmed using fluorescence correlation spectroscopy. A sensitive assay based on single lipid tracking experiments on a planar solid-supported phospholipid bilayer is presented that establishes conditions of monovalent conjugation of QDs to lipids. The QD-lipids are then employed as single-molecule tracking probes in plasma membranes of several cell types. Initial tracking experiments at a frame rate of 30 frames/s corroborate that QD-lipids diffuse like dye-labeled lipids in the plasma membrane of COS-7, HEK-293, 3T3, and NRK cells, thus confirming monovalent labeling. Finally, QD-lipids are applied for the first time to high-speed single-molecule imaging by tracking their lateral mobility in the plasma membrane of NRK fibroblasts with up to 1000 frames/s. Our high-speed tracking data, which are in excellent agreement with previous tracking experiments that used larger (40 nm) Au labels, not only push the time resolution in long-time, continuous fluorescence-based single-molecule tracking but also show that highly photostable, photoluminescent nanoprobes of 10 nm size can be employed (AEE-coated QDs). These probes are also attractive because, unlike Au nanoparticles, they facilitate complex multicolor experiments.
Principles of mixed-initiative user interfaces (1999)

Recent debate has centered on the relative promise of focusing user-interface research on developing new metaphors and tools that enhance users ’ abilities to directly manipulate objects versus directing effort toward developing interface agents that provide automation. In this paper, we review principles that show promise for allowing engineers to enhance human-computer interaction through an elegant coupling of automated services with direct manipulation. Key ideas will be highlighted in terms of the Lookout system for scheduling and meeting management.
The Black/White Binary Paradigm of Race: The Normal Science of American Racial Thought (1997)

The Black/White Binary Paradigm of race has become the subject of increasing interest and scrutiny among some scholars of color. This Article uses Thomas Kuhn’s notions of paradigm and the properties of paradigms to explore several leading works on race. The works the author explores demonstrate the Black/White paradigm of race and some of its properties, among them extensive paradigm elaboration over the years. Paradigms have limitations, however. Among them is a tendency to truncate history for the sake of telling a linear story of progress. The author demonstrates how one constitutional law text truncates history, by omitting entirely Mexican-American struggles for desegregation, and presenting a linear story of the Black struggle for civil rights. Omitting important history from the narrative of civil rights history becomes extraordinarily damaging, since it distorts history and contributes to the marginalization of non-Black peoples of color. While recognizing the centrality of slavery and White racism against Blacks at the core of American history and society, this Article seeks to expand our understanding of racism through the use of legal history. The author contends that mutual and particularized understanding of racism as it affects all people of color has the potential to enhance our abilities to understand each other and to join together to fight the common evil of racism.
Signalling via type IA and type IB bone morphogenetic protein receptors (BMPR) regulates intramembranous bone formation, chondrogenesis and feather formation in the chicken embryo. (2002)

Bone morphogenetic proteins (BMPs) signal via complexes of type I and type II receptors. In this study, we mapped the expression of type IA, type IB and type II receptors during craniofacial chondrogenesis and then perturbed receptor function in vivo with retroviruses expressing dominant-negative or constitutively active type I receptors. BmprIB was the only receptor expressed within all cartilages. BmprIA was initially expressed in cartilage condensations, but later decreased within cartilage elements. BmprII was expressed at low levels in the nasal septum and prenasal cartilage and at higher levels in other craniofacial cartilages. The maxillary prominence, which gives rise to several intramembranous bones, expressed both type I receptors. Misexpression of dnBMPRIB decreased the size of cartilages and bones on the treated side. In contrast, dnBMPRIA had no effect on the skeletal phenotype. The phenotypes of caBMPRIA and caBMPRIB were similar; both led to overgrowth of cartilage elements, thinner bones with fewer trabeculae and inhibition of feather development. Infection with constitutively active viruses resulted in ectopic expression of Msx1, Msx2 and Fgfr2 throughout the maxillary mesenchyme. These data suggest that the pattern of trabeculation in membranous bones derived from the maxillary prominence was related to the change in expression pattern and that Msx and Fgfr2 genes were downstream of both type I BMP receptors. We conclude that the requirement for the type IB is greater than for the type IA receptor but, when active, both receptors play similar roles in regulating bone, cartilage and feather formation in the skull.
Narrowing of the palladium-hydrogen miscibility gap in nanocrystalline palladium (1993)

In situ x-ray-diffraction studies of the hydriding behavior of coarse-grained and nanocrystalline palladium samples at ambient temperature are descibed. A previously observed narrowing of the miscibility gap in nanocrystalline palladium was reproduced. The present results, however, demonstrate that this change in the palladium-hydrogen phase diagram for nanocrystalline material is not related to an inability to form the hydride phase in highly disordered grain boundary regions as previously proposed. Instead, the entire volume of nanocrystalline samples was observed to transform to \ensuremath{\beta}-PdH upon exposure to hydrogen. This behavior indicates that the entropy and/or enthalpy of mixing for the palladium-hydrogen system differs in nanocrystalline and coarse-grained materials. Because of these changes in thermodynamic quantities, the phase boundary of the palladium-hydrogen miscibility gap is predicted to be shifted to lower temperatures for nanocrystalline samples.
Oncogenes, ions, and phospholipids (1985)

Recent discoveries in tumor virology, lipid biochemistry, and ion transport studies promise to revolutionize our understanding of cell proliferation, differentiation, and tumorigenesis. A model is proposed, based on similar schemes presented recently by others, that incorporates these discoveries and provides a focus for future research on the functions of oncogene proteins. The model suggests that the early (competence) events in the initiation of cell proliferation are triggered by activation of phosphatidylinositol (PI) turnover, which releases two second messengers, 1,2-diacylglycerol (1,2-DG) and inositol-1,4,5-trisphosphate (IP3). PI turnover is proposed to be regulated by the oncogene protein kinases (src, ros, abl, fps) either directly (acting as PI kinases) or indirectly (as tyrosine kinases). The IP3 triggers Ca2+ release from internal stores, and the elevation of cytosolic Ca2+ acts synergistically with 1,2-DG to activate the Ca2+- and phospholipid-dependent kinase C. Kinase C copurifies with the receptor for the tumor-promoting phorbol esters. It is suggested that kinase C then activates the Na+-H+ exchange system, resulting in an elevation of cytosolic pH and Na+, and that these ionic signals (including the change in Ca2+), either in concert or individually, induce further events, including expression of the protooncogene c-myc, which together commit the cell to initiate replication. Evidences in support of this model are reviewed, together with complications indicating its present inadequacies, particularly recent data suggesting that 1,2-DG may activate tyrosine kinases independent of kinase C.
Construction of a novel artificial-ribozyme-releasing plasmid (1990)

A novel 'active-ribozyme-releasing system' was constructed, taking advantage of the consensus sequence of a new class of ribozyme. An active ribozyme sequence, targeted for the SFL1 gene (a yeast suppressor gene for flocculation) was fused just downstream of the T7 promoter. The 3' terminus of the first ribozyme was designed to be trimmed by the second ribozyme connected to the downstream of the first active ribozyme. In vitro experiments revealed that the active ribozyme targeted to SFL1 was successfully released by the action of the second ribozyme, subsequently cleaving the SFL1 mRNA at the predetermined site. Since the first active ribozyme with a defined 3'-terminus can be produced even when a circular DNA is used as a template, this kind of construct has a potential to release an 'active ribozyme' tailored to destroy a target gene (RNA) in vivo. Moreover, the second ribozyme in this construct can be utilized as a universal pseudo-terminator for generation of any RNA transcripts inserted in place of the cassette portion of the first ribozyme.
Immunohistochemical determination of complement activation in joint tissues of patients with rheumatoid arthritis and osteoarthritis using neoantigen-specific monoclonal antibodies. (1992)

Murine monoclonal antibodies specific for neoepitopes expressed by C9 incorporated into membrane attack complexes and by membrane-bound C3b and iC3b have been prepared and characterised. These reagents were used to determine the extent and locus of complement activation in synovial-tissues obtained from patients with rheumatoid arthritis and osteoarthritis. In the four rheumatoid arthritis patients there was extensive deposition of C3 activation products and C5b-9 complexes onto the synovial membrane and the pattern of deposition of both neoantigens in serial tissue sections was very similar. There was less extensive staining for C3 and, particularly, C9 neoepitopes on the apical surface of vessel endothelia. In two of four osteoarthritic patients a similar pattern of C3 and C9 neoepitope deposition was found; in the remaining patients no C5b-9 could be located. Synovial vessel walls, but not synovial cells, from both groups of patients stained extensively for the complement regulatory protein CD59. In synovial membranes from patients with osteoarthritis, C9 appeared to be present predominantly in SC5b-9 complexes whereas in rheumatoid arthritis patients no evidence of S-protein incorporation into membrane attack complexes could be demonstrated, suggesting that in rheumatoid arthritis there is damage to the synovial membrane as a result of complement activation and C5b-9 deposition.
Recent developments in the chemistry of dihydropyridines (2002)

A graphical abstract is available for this content
High-throughput scanning with single-molecule sensitivity (2005)

We report on the application of a novel fluorescence-microscope based scanning device with single molecule sensitivity to microarray readout. The device is based on a CCD camera operated in time delay and integration (TDI) mode synchronized with the movement of a sample scanning stage, enabling continuous data acquisition. The implementation of a focus hold system keeps the sample in focus during scanning. Results from ultra-sensitive high-resolution microarray readout provide clear evidence for the superiority of the novel detection method over conventional microarray readout systems in particular regarding to sensitivity and dynamic range. Minute sample amount and lacking amplification methods will demand for this ultra-sensitive readout technology in future genomic and proteomic research.