gebhart/patrepeval huggingface dataset:
Microsphere‐induced embolic stroke: An MRI study (2004)

Despite the many studies of the middle cerebral artery occlusion (MCAO) model, efficient therapy for stroke is still lacking, emphasizing the need for further development and characterization of experimental stroke models. In the present study, the rather unexplored multifocal microsphere-induced stroke model in rats was characterized by multiparametric MRI. We induced microembolic infarction in a group of Sprague-Dawley rats by injecting a dose of about 1000 50-microm polyethylene microspheres intracranially from the external carotid artery. Diffusion-, perfusion-, and T(2)-weighted MRI were used to evaluate the infarct development during and following the first 3 hr after microsphere injection (N = 20). The animals were also imaged at 12-hr (N = 8), 24-hr (N = 17), and 48-hr (N = 5) time points. After the final imaging time point, the brains were removed and sectioned into 2-mm-thick slices, and infarct volumes were measured by 2,3,4-triphenyltetrazolium chloride (TTC) staining. From calculated apparent diffusion coefficient (ADC) maps, a volume of reduced ADC appeared 0.5-1.0 hr postinjection, and by the 3-hr time point the volume of ADC reduction had increased to a size of 5% +/- 1% (mean +/- SEM) of the brain hemisphere. The lesion volume increased significantly (P < 0.01) to 16% +/- 2% of the hemisphere volume at the 12-hr time point, while at 24 hr the lesion (15% +/- 2% of the hemisphere) was also significantly larger (P < 0.001) than at 3 hr. The perfusion deficit resulting from the microsphere injection was immediate, going from a cerebral blood flow index (CBF(i)) of 74% +/- 3% at the time of microsphere injection to 68% +/- 2% of the contralateral mean at 3 hr (P < 0.05), to 55% +/- 4% of the contralateral values at 12 hr (P < 0.05), and to 57% +/- 2% of the contralateral mean at 24 hr (P < 0.001). The lesion development in the microsphere-induced stroke model was found to be slower than in the MCAO model, and continued up to the 24-48-hr time point.
Trastuzumab and pertuzumab plant biosimilars: Modification of Asn297-linked glycan of the mAbs produced in a plant with fucosyltransferase and xylosyltransferase gene knockouts (2017)

Plant biosimilars of anticancer therapeutic antibodies are of interest not only because of the prospects of their practical use, but also as an instrument and object for study of plant protein glycosylation. In this work, we first designed a pertuzumab plant biosimilar (PPB) and investigated the composition of its Asn297-linked glycan in comparison with trastuzumab plant biosimilar (TPB). Both biosimilars were produced in wild-type (WT) Nicotiana benthamiana plant (PPB-WT and TPB-WT) and transgenic ΔXTFT N. benthamiana plant with XT and FT genes knockout (PPB-ΔXTFT and TPB-ΔXTFT). Western blot analysis with anti-α1,3-fucose and anti-xylose antibodies, as well as a test with peptide-N-glycosidase F, confirmed the absence of α1,3-fucose and xylose in the Asn297-linked glycan of PPB-ΔXTFT and TPB-ΔXTFT. Peptide analysis followed by the identification of glycomodified peptides using MALDI-TOF/TOF showed that PPB-WT and TPB-WT Asn297-linked glycans are mainly of complex type GnGnXF. The core of PPB-WT and TPB-WT Asn297-linked GnGn-type glycan contains α1,3-fucose and β1,2-xylose, which, along with the absence of terminal galactose and sialic acid, distinguishes these plant biosimilars from human IgG. Analysis of TPB-ΔXTFT total carbohydrate content indicates the possibility of changing the composition of the carbohydrate profile not only of the Fc, but also of the Fab portion of an antibody produced in transgenic ΔXTFT N. benthamiana plants. Nevertheless, study of the antigen-binding capacity of the biosimilars showed that absence of xylose and fucose residues in the Asn297-linked glycans does not affect the ability of the glycomodified antibodies to interact with HER2/neu positive cancer cells.
Saccharomyces cerevisiae Glutaredoxin 5-deficient Cells Subjected to Continuous Oxidizing Conditions Are Affected in the Expression of Specific Sets of Genes (2004)

The Saccharomyces cerevisiae GRX5 gene codes for a mitochondrial glutaredoxin involved in the synthesis of iron/sulfur clusters. Its absence prevents respiratory growth and causes the accumulation of iron inside cells and constitutive oxidation of proteins. Null Deltagrx5 mutants were used as an example of continuously oxidized cells, as opposed to situations in which oxidative stress is instantaneously caused by addition of external oxidants. Whole transcriptome analysis was carried out in the mutant cells. The set of genes whose expression was affected by the absence of Grx5 does not significantly overlap with the set of genes affected in respiratory petite mutants. Many Aft1-dependent genes involved in iron utilization that are up-regulated in a frataxin mutant were also up-regulated in the absence of Grx5. BIO5 is another Aft1-dependent gene induced both upon iron deprivation and in Deltagrx5 cells; this links iron and biotin metabolism. Other genes are specifically affected under the oxidative conditions generated by the grx5 mutation. One of these is MLP1, which codes for a homologue of the Slt2 kinase. Cells lacking MLP1 and GRX5 are hypersensitive to oxidative stress caused by external agents and exhibit increased protein oxidation in relation to single mutants. This in turn points to a role for Mlp1 in protection against oxidative stress. The genes of the Hap4 regulon, which are involved in respiratory metabolism, are down-regulated in Deltagrx5 cells. This effect is suppressed by HAP4 overexpression. Inhibition of respiratory metabolism during continuous moderately oxidative conditions could be a protective response by the cell.
Stimulation of human vascular endothelial cell growth by a platelet‐derived growth factor and thrombin (1979)

Repair of a vascular wound is mediated by migration and subsequent replication of the endothelial cells that form the inner lining of blood vessels. We have measured the growth response of human umbilical vein endothelial cells (HuE) to two polypeptides that are transiently produced in high concentrations at the site of a wound; the platelet-derived growth factor (PDGF) and the protease thrombin. When 10(4) HuE cells are seeded as a dense island (2-mm diameter) in the center of a 16-mm tissue culture well in medium containing 20% human serum derived from platelet-poor plasma (PDS), no increase in cell number or colony size is observed. With the addition of 0.5 ng/ml partially purified PDGF, colony size increases and the number of cells after 8 days is 4.8 X 10(4). When human thrombin (1 microgram/ml) is added along with the PDGF, the cell number rises to 9.2 X 10(4). Thrombin alone stimulates no increase in cell number. Although partially purified PDGF stimulates endothelial cells maintained in PDS as well as those maintained in whole blood serum (WBS), pure PDGF is active only when assayed in medium that contains WBS and is supplemented with thrombin. These results suggest the existence of a second class of platelet-derived factors that enable HuE cells to respond to the mitogenic activity of the purified platelet mitogen and thrombin.
Human Naive CD4 T-Cell Clones Specific for HIV Envelope Persist for Years In Vivo in the Absence of Antigenic Challenge (2005)

To study the persistence of HIV-specific human naive CD4-lymphocytes in vivo in the absence of antigenic stimulation, we identified 2 HIV-seronegative low-risk subjects carrying CD4-cells specific for gp120 that could be expanded in vitro. CD4 T-cell lines specific for gp120 were generated by stimulation cycles with antigen-pulsed antigen-presenting cells. Clonal analysis was performed by spectratyping and by sequencing of the CDR3 regions of the BV and AV-T-cell receptor (TCR) genes. HIV-specific T cells were expanded in vitro in 1989 and 2004. These lines were generated from naive precursors. Analysis of TCR-BV gene family use and sequencing of the TCR-BV22 hypervariable region revealed a BV22 clonotype in the 1989 line. The BV22-CDR3-based polymerase chain reaction primer confirmed that the 1989 and 2004 T-cell lines contained the same clonotype. In addition, the 1989 and 2004 T cells used the same TCR-AV38 gene family and identical CDR3-AV regions, confirming clonal identity. Similar data for a persistent clonotype defined by BV CDR3 sequencing were obtained from the second subject. In conclusion, naive CD4-cells specific for an HIV antigen not encountered in vivo persisted for more than 10 to 15 years. An extended lifespan, homeostatic proliferation, or the ability of the thymus to issue the same CD4 T-cell clone reiteratively might account for the phenomenon.
Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases (2010)

A cardinal feature of inflammation is the tissue recruitment of leukocytes, a process that is mediated predominantly by chemokines via their receptors on migrating cells. CCR2 and CCR5, two CC chemokine receptors, are important players in the trafficking of monocytes/macrophages and in the functions of other cell types relevant to disease pathogenesis. This review provides a brief overview of the biological actions of CCR2 and CCR5 and a comprehensive summary of published data that demonstrate the involvement of both receptors in the pathogenesis of immunologic diseases (RA, CD, and transplant rejection) and cardiovascular diseases (atherosclerosis and AIH). In light of the potential for functional redundancy of chemokine receptors in mediating leukocyte trafficking and the consequent concern over insufficient efficacy offered by pharmacologically inhibiting one receptor, this review presents evidence supporting dual targeting of CCR2 and CCR5 as a more efficacious strategy than targeting either receptor alone. It also examines potential safety issues associated with such dual targeting.
Adhesion barriers of carboxymethylcellulose and polyethylene oxide composite gels (2002)

Composite gels and films of CMC and PEO have been used to separate healing tissues and have been demonstrated to reduce postsurgical adhesions in animal models of adhesion formation. Gels of CMC/PEO were studied here to elucidate the mechanism by which the combination of PEO with CMC is effective in reducing adhesions between tissues. CMC and PEO were demonstrated to undergo micro phase separation to form a two-phase system. Protein partitioning was measured in this system for albumin, fibrinogen, and gamma globulin. All of these proteins were found to partition preferentially into the CMC phase. When gels of CMC and PEO were examined for tissue adherence, the addition of PEO reduced the adherence of CMC to tissues. To further investigate the effects of PEO on tissue adherence of the gel, the extent of thrombus formation of citrated blood initiated by calcium chloride in CMC/PEO gels was measured in vitro. The extent of thrombus formation by CMC was reduced proportionally to the content of PEO in gels of CMC/PEO. A model was developed to explain how CMC and PEO contribute to the effectiveness of CMC/PEO gels that form a barrier between healing tissues to reduce postsurgical adhesions. In an open system PEO is released from the gel faster than CMC is dissolved, resulting in a shell structure with CMC coated by PEO. The PEO-rich outer layer functions to inhibit protein deposition and thrombus formation. The CMC-rich layer functions to anchor the gel to the tissue surface.
Crystal Structure of the Human K2P TRAAK, a Lipid- and Mechano-Sensitive K + Ion Channel (2012)

TRAAK channels, members of the two-pore domain K(+) (potassium ion) channel family K2P, are expressed almost exclusively in the nervous system and control the resting membrane potential. Their gating is sensitive to polyunsaturated fatty acids, mechanical deformation of the membrane, and temperature changes. Physiologically, these channels appear to control the noxious input threshold for temperature and pressure sensitivity in dorsal root ganglia neurons. We present the crystal structure of human TRAAK at a resolution of 3.8 angstroms. The channel comprises two protomers, each containing two distinct pore domains, which create a two-fold symmetric K(+) channel. The extracellular surface features a helical cap, 35 angstroms tall, that creates a bifurcated pore entryway and accounts for the insensitivity of two-pore domain K(+) channels to inhibitory toxins. Two diagonally opposed gate-forming inner helices form membrane-interacting structures that may underlie this channel's sensitivity to chemical and mechanical properties of the cell membrane.
Synthesis of substituted benzamides and benzimidazoles as anthelmintic and antimicrobial agents. (1982)

The synthesis and biological activity of a series of substituted benzamides (5-8, 14-17) 3,5-dinitrobenzoic acids (12, 13, 18) and benzimidazoles (9-11, 19-21) are described. Compounds 5, 6, 7, 12 and 14 showed 40-50% clearance of Nippostrongylus brasiliensis in rats at a dose of 250 mg/kg given daily for 3 d while a few compounds inhibited the growth of various strains of bacteria and fungi.
Asymmetric catalysis. Production of chiral diols by enantioselective catalytic intramolecular hydrosilation of olefins (1992)

Rhodium(1) chiral diphosphine complexes efficiently and rapidly catalyze the intramolecular hydrosilation of silyl&#13;\nethers derived from allylic alcohols. The efficiency and rates of intramolecular hydrosilations were determined for a variety&#13;\nof silyl and olefin substituents. The catalysts were found to tolerate a wide variety of silyl substituents, although terminal&#13;\nalkyl olefin substituents were found to retard catalysis. Terminal aryl olefin substituents were found to be hydrosilated efficiently&#13;\nand at reasonable rates. One of the chiral catalysts is highly enantioselective for terminal aryl olefin substituents. Almost&#13;\nquantitative eels are obtained. Moreover, the ee’s are only slightly sensitive to aryl and olefin substituents, suggesting that&#13;\nthis enantioselective catalysis can provide a wide range of chiral species. Oxidative cleavage of the hydrosilation products&#13;\ngives chiral diols.
<em>Lactuca virosa</em>, a source of disease resistance genes for lettuce breeding: results and difficulties for gene introgression (2003)

Eucarpia Meeting on Leafy Vegetables Genetics and Breeding Noordwijkerhout, NLD (2003-03-19 - 2003-03-21). Wageningen, NLD : CGN. 61-67
Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence. (1998)

The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.
Don't link me in (1991)

is often described as nodes of information with links between them, suggesting the conceptual model of a graph. A broader definition is a system of nodes of information through which people can move nonlinearly. Such a definition, while including graph-based hypermedia, also allows alternative implementations.
Macrophage Differentiation Inducing Factor from Human Monocytic Cells Is Equivalent to Murine Leukemia Inhibitory Factor (1989)

Human macrophage differentiation inducing factor (DIF) can induce differentiation of human myeloid leukemic cells into macrophage-like cells in vitro. A procedure is described for purification of DIF from serum-free human monocytic leukemia THP-1 cell-conditioned medium. The procedure included concentration of a conditioned medium by ultrafiltration, lentil lectin-Sepharose affinity chromatography, and fast protein liquid chromatography using Mono S and Mono Q. DIF-A of pI 9.0 and DIF-B of pI 8.8 were obtained after a final purification with a Mono Q column, and both DIF gave a single peak with a molecular weight of approximately 51,000 determined by gel chromatography. NH2-terminal amino acid analysis of DIF-A showed a noticeable homology with murine leukemia inhibitory factor. Human DIF-A was found to induce maturation of human and murine leukemic cells into both macrophage-like cells with nitro blue tetrazolium reducing activity and phagocytic cells, but was found to suppress proliferation of these leukemic cells.
Genetic and epigenetic inactivation of LPL gene in human prostate cancer (2008)

Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p=0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer.
Variable-focus lens with 1-kHz bandwidth (2004)

This paper proposes a variable-focus lens with 1-kHz bandwidth. The lens transforms its shape rapidly using the liquid pressure generated by a piezo stack actuator. This mechanism also includes a built-in motion amplifier with high bandwidth to compensate for the short working range of the piezo stack actuator. Prototypes have been developed to validate the proposed design. A 1-kHz bandwidth of the lenses was confirmed by measuring the frequency responses. Refractive power ranging from -1/167 to 1/129 mm(-1) and a maximum resolution of 12.3 cycles/mm were attained.
Self-Assembled Quantum Dot-Sensitized Multivalent DNA Photonic Wires (2010)

Combining the inherent scaffolding provided by DNA structure with spatial control over fluorophore positioning allows the creation of DNA-based photonic wires with the capacity to transfer excitation energy over distances greater than 150 Å. We demonstrate hybrid multifluorophore DNA-photonic wires that both self-assemble around semiconductor quantum dots (QDs) and exploit their unique photophysical properties. In this architecture, the QDs function as both central nanoscaffolds and ultraviolet energy harvesting donors that drive Förster resonance energy transfer (FRET) cascades through the DNA wires with emissions that approach the near-infrared. To assemble the wires, DNA fragments labeled with a series of increasingly red-shifted acceptor-dyes were hybridized in a predetermined linear arrangement to a complementary DNA template that was chemoselectively modified with a hexahistidine-appended peptide. The peptide portion facilitated metal-affinity coordination of multiple hybridized DNA-dye structures to a central QD completing the final nanocrystal-DNA photonic wire structure. We assembled several such hybrid structures where labeled-acceptor dyes were excited by the QDs and arranged to interact with each other via consecutive FRET processes. The inherently facile reconfiguration properties of this design allowed testing of alternate formats including the addition of an intercalating dye located in the template DNA or placement of multiple identical dye acceptors that engaged in homoFRET. Lastly, a photonic structure linking the central QD with multiple copies of DNA hybridized with 4-sequentially arranged acceptor dyes and demonstrating 4-consecutive energy transfer steps was examined. Step-by-step monitoring of energy transfer with both steady-state and time-resolved spectroscopy allowed efficiencies to be tracked through the structures and suggested that acceptor dye quantum yields are the predominant limiting factor. Integrating such DNA-based photonic structures with QDs can help create a new generation of biophotonic wire assemblies with widespread potential in nanotechnology.
Extended depth-of-focus 3D micro integral imaging display using a bifocal liquid crystal lens (2015)

We present a three dimensional (3D) micro integral imaging display system with extended depth of focus by using a polarized bifocal liquid crystal lens. This lens and other optical components are combined as the relay optical element. The focal length of the relay optical element can be controlled to project an elemental image array in multiple positions with various lenslet image planes, by applying different voltages to the liquid crystal lens. The depth of focus of the proposed system can therefore be extended. The feasibility of our proposed system is experimentally demonstrated. In our experiments, the depth of focus of the display system is extended from 3.82 to 109.43&#xA0;mm.
Learning long-term dependencies with gradient descent is difficult (1994)

Recurrent neural networks can be used to map input sequences to output sequences, such as for recognition, production or prediction problems. However, practical difficulties have been reported in training recurrent neural networks to perform tasks in which the temporal contingencies present in the input/output sequences span long intervals. We show why gradient based learning algorithms face an increasingly difficult problem as the duration of the dependencies to be captured increases. These results expose a trade-off between efficient learning by gradient descent and latching on information for long periods. Based on an understanding of this problem, alternatives to standard gradient descent are considered.
Further evidence on the protein complexes of some hyaluronic acids (1958)

This work follows from that of Blumberg & Ogston (1957). They showed that papain is a specific agent for degrading the protein part of the hyaluronic acid complex isolated from ox synovial fluid by filtration This is associated with a marked decrease in the molecular weight and the hydrodynamic specific volume as well as changes irn other physical characteristics, which indicate that the material has been depolymerized.