gebhart/patrepeval huggingface dataset:
Biosynthesis of heparin. The d-glucuronosyl- and N-acetyl-d-glucosaminyltransferase reactions and their relation to polymer modification (1992)

Oligosaccharides with the general structure [GlcA-GlcNAc]n-GlcA-aMan (aMan is 2,5-anhydro-D-mannose), derived from the Escherichia coli K5 capsular polysaccharide, were found to serve as monosaccharide acceptors for a GlcNAc-transferase, solubilized from a mouse mastocytoma microsomal fraction and implicated in heparin biosynthesis. Digestion of these oligosaccharides with beta-D-glucuronidase yielded acceptors for the GlcA-transferase that acts in concert with the GlcNAc-transferase. Assays based on the oligosaccharide acceptors showed broad pH optima for the two enzymes, centred around pH 6.5 for the GlcNAc-transferase and around pH 7.0 for the GlcA-transferase. The GlcNAc-transferase showed an absolute requirement for Mn2+, whereas the GlcA-transferase was stimulated by Ca2+ and Mg2+ but not by Mn2+. The GlcNAc acceptor ability of the [GlcA-GlcNAc]n-GlcA-aMan oligosaccharides increased with increasing chain length, as reflected by the apparent Km, which was 60 microM for a hexasaccharide but 6 microM for a hexadecasaccharide. By contrast, the Km for [GlcNAc-GlcA]n-aMan oligosaccharides in the GlcA-transferase reaction was higher, approximately 0.5 mM, and unaffected by acceptor size. After chemical modification of the oligosaccharides to obtain mixed N-substituents (N-unsubstituted, N-acetylated or N-sulphated GlcN residues), GlcNAc transfer was found to be virtually independent of the N-substituent pattern of the acceptor sequence. The GlcA-transferase, on the other hand, showed marked preference for an acceptor with a non-reducing-terminal GlcNAc-GlcA-GlcNSO3- sequence, which would thus have a lower Km for the enzyme than the corresponding fully N-acetylated structure. These results, along with our previous finding that chain elongation in a mastocytoma microsomal system is strongly promoted by concomitant N-sulphation of the nascent chain [Lidholt, Kjellén & Lindahl (1989) Biochem. J. 261, 999-1007], raise the possibility that the glycosyltransferases and the N-deacetylase/N-sulphotransferase act in concert during chain elongation, assembled into an enzyme complex.
Biomolecular markers of breast cancer (2006)

Here, the structure, function, biological and pathological significance and clinical utility of the principal biomolecular markers of breast cancer is reviewed. Each marker was scored for clinical utility using a recently developed tumor marker utility grading system (TMUGS). Among the tissue markers, ERs and PRs are important prognostic/predictive factors and the only tissue markers routinely determined. ER cross-talks with other growth factors while co-regulatory factors enhance (co-activators) or decrease (co-repressors) its transcriptional activity. C-erbB-2 and Ki67/MIB-1 select for adjuvant chemotherapy a subgroup of lymph-node negative patients at a high risk of relapse. Monoclonal antibodies (trastuzumab, gefitinib, erlotinib and bevacizumab) targeting tissue markers and involved in tumor growth and metastasization (EGFR, C-erbB-2, VEGF) have been developed; they showed therapeutical single agent activity as well as potent synergy with chemotherapy agents in metastatic cancer. Among circulating markers, some are potentially useful in the early detection and monitoring of metastatic disease; nevertheless, none is routinely recommended. To suspect distant metastases, CEA-TPA-CA15.3 panel attained accuracy of about 90%. ECD HER2-neu, p53 and nucleophosmin antibodies seem suitable candidates for different associations. Preliminary observations suggest that an early detection with tumor markers and successive treatment of relapses significantly prolongs disease-free and overall survival in selected patients. In conclusion, biomolecular markers are improving understanding of biology and management of breast cancer.
Antibody-protein interactions: benchmark datasets and prediction tools evaluation (2007)

It may be possible to improve epitope prediction methods through training on datasets which include only immune epitopes and through utilizing more features characterizing epitopes, for example, the evolutionary conservation score. Notwithstanding, overall poor performance may reflect the generality of antigenicity and hence the inability to decipher B-cell epitopes as an intrinsic feature of the protein. It is an open question as to whether ultimately discriminatory features can be found.
Three dimensional visualization by photon counting computational Integral Imaging (2008)

In this paper, we present three dimensional (3D) object reconstruction using photon-counted elemental images acquired by a passive 3D Integral Imaging (II) system. The maximum likelihood (ML) estimator is derived to reconstruct the irradiance of the 3D scene pixels and the reliability of the estimator is described by confidence intervals. For applications in photon scarce environments, our proposed technique provides 3D reconstruction for better visualization as well as significant reduction in the computational burden and required bandwidth for transmission of integral images. The performance of the reconstruction is illustrated qualitatively and compared quantitatively with Peak to Signal to Noise Ratio (PSNR) criterion.
Geometric manipulation of the high-field linear magnetoresistance in InSb epilayers on GaAs (001) (2005)

We address the inherent high-field magnetoresistance (MR) of indium antimonide epilayers on GaAs (001), studying the modification of the MR when processed into a set of geometries. The changes produced by the geometries are quite subtle. The extraordinary MR geometry produces the highest low-field MR while the Corbino geometry produces the largest high-field magnetoresistance. We demonstrate that any material with an unsaturating linear intrinsic MR, will also have an unsaturating linear Corbino MR, and that the ideal material for linear MR sensors in conventional geometries would have a high mobility and a small, linear intrinsic MR.
Visualization of protein interactions in living plant cells using bimolecular fluorescence complementation (2004)

Dynamic networks of protein-protein interactions regulate numerous cellular processes and determine the ability to respond appropriately to environmental stimuli. However, the investigation of protein complex formation in living plant cells by methods such as fluorescence resonance energy transfer has remained experimentally difficult, time consuming and requires sophisticated technical equipment. Here, we report the implementation of a bimolecular fluorescence complementation (BiFC) technique for visualization of protein-protein interactions in plant cells. This approach relies on the formation of a fluorescent complex by two non-fluorescent fragments of the yellow fluorescent protein brought together by association of interacting proteins fused to these fragments (Hu et al., 2002). To enable BiFC analyses in plant cells, we generated different complementary sets of expression vectors, which enable protein interaction studies in transiently or stably transformed cells. These vectors were used to investigate and visualize homodimerization of the basic leucine zipper (bZIP) transcription factor bZIP63 and the zinc finger protein lesion simulating disease 1 (LSD1) from Arabidopsis as well as the dimer formation of the tobacco 14-3-3 protein T14-3c. The interaction analyses of these model proteins established the feasibility of BiFC analyses for efficient visualization of structurally distinct proteins in different cellular compartments. Our investigations revealed a remarkable signal fluorescence intensity of interacting protein complexes as well as a high reproducibility and technical simplicity of the method in different plant systems. Consequently, the BiFC approach should significantly facilitate the visualization of the subcellular sites of protein interactions under conditions that closely reflect the normal physiological environment.
An electromigration failure model for interconnects under pulsed and bidirectional current stressing (1994)

An electromigration failure model which can be used to project the electromigration lifetime under pulsed DC and AC current stressing has been reported. The experimental results indicate that different metallization systems (Al-2%Si, Al4%Cu/TiW, and Cu) show similar failure behaviors, which can be explained and predicted by this model. The pulsed DC lifetime is found to be longer than DC lifetime, and the AC lifetime is found to be very much longer. This recognition can provide significant relief to circuit designs involving metals carrying pulsed DC and AC currents, and allow a more aggressive design to improve circuit density and speed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhancing the performance of the light field microscope using wavefront coding (2014)

Light field microscopy has been proposed as a new high-speed volumetric computational imaging method that enables reconstruction of 3-D volumes from captured projections of the 4-D light field. Recently, a detailed physical optics model of the light field microscope has been derived, which led to the development of a deconvolution algorithm that reconstructs 3-D volumes with high spatial resolution. However, the spatial resolution of the reconstructions has been shown to be non-uniform across depth, with some z planes showing high resolution and others, particularly at the center of the imaged volume, showing very low resolution. In this paper, we enhance the performance of the light field microscope using wavefront coding techniques. By including phase masks in the optical path of the microscope we are able to address this non-uniform resolution limitation. We have also found that superior control over the performance of the light field microscope can be achieved by using two phase masks rather than one, placed at the objective's back focal plane and at the microscope's native image plane. We present an extended optical model for our wavefront coded light field microscope and develop a performance metric based on Fisher information, which we use to choose adequate phase masks parameters. We validate our approach using both simulated data and experimental resolution measurements of a USAF 1951 resolution target; and demonstrate the utility for biological applications with in vivo volumetric calcium imaging of larval zebrafish brain.
In-vivo testing of digital cellular telephones in patients with implantable cardioverter-defibrillators (2001)

Digital cellular telephones do not represent a risk to Medtronic and Guidant/CPI recipients of the specific implantable defibrillator models herein tested.
Klotho Coreceptors Inhibit Signaling by Paracrine Fibroblast Growth Factor 8 Subfamily Ligands (2012)

It has been recently established that Klotho coreceptors associate with fibroblast growth factor (FGF) receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here, we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FGF19 or FGF21) and FGFR independently through two distinct binding sites. FGF19 and FGF21 use their respective C-terminal tails to bind to a common binding site on βKlotho. Importantly, we also show that Klotho coreceptors engage a conserved hydrophobic groove in the immunoglobulin-like domain III (D3) of the "c" splice isoform of FGFR. Intriguingly, this hydrophobic groove is also used by ligands of the paracrine-acting FGF8 subfamily for receptor binding. Based on this binding site overlap, we conclude that while Klotho coreceptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR.
Sequence-specific DNA Binding and Transcriptional Regulation by the Promyelocytic Leukemia Zinc Finger Protein (1997)

Chromosomal translocation t(11;17)(q23;21) is associated with a retinoic acid-resistant form of acute promyelocytic leukemia. The translocation fuses the RARalpha gene to the PLZF gene, resulting in the formation of reciprocal fusion proteins, hypothesized to play prominent roles in leukemogenesis. Promyelocytic leukemia zinc finger (PLZF) encodes a transcription factor with nine Krüppel-like zinc fingers, seven of which are retained in the t(11;17) fusion protein RARalpha-PLZF. We identified a specific DNA-binding site for the PLZF protein and showed that PLZF binds to this site through its most carboxyl seven zinc fingers. In co-transfection experiments, PLZF repressed transcription through its cognate binding site. This repression function of PLZF was mapped to two regions on the protein, including the evolutionarily conserved POZ domain. In contrast, the RARalpha-PLZF protein activated transcription of a promoter containing a PLZF response element. These results suggest that RARalpha-PLZF, generated in acute promyelocytic leukemia, is an aberrant transcription factor that can deregulate the expression of PLZF target genes and contribute to leukemogenesis.
Clinical studies with and pharmacokinetic considerations of sustained-release levodopa. (1992)

Although levodopa is the most effective antiparkinson agent yet available, strategies for improving the constancy of levodopa delivery to the brain are sometimes needed to optimize its actions. Its most common formulation is Sinemet, a combination of levodopa and carbidopa. Conventional Sinemet is absorbed and metabolized over 3 to 4 hours; however, Sinemet CR, a sustained-release preparation of 200 mg of levodopa and 50 mg of carbidopa, offers a duration of effect almost double that of Sinemet 25/100. In an 8-week trial with 25 parkinsonian patients, those treated with Sinemet CR required fewer daily doses than with the conventional Sinemet formulation and experienced improved "on" times (although improvements were not evident in all motor-fluctuation situations). The best therapeutic strategy may be a combination of the two Sinemet preparations, conventional Sinemet 25/100 as a booster dose and Sinemet CR for more sustained effect.
Broad Humoral and Cellular Immunity Elicited by a Bivalent DNA Vaccine Encoding HA and NP Genes from an H5N1 Virus (2011)

Influenza A virus is highly variable and a major viral respiratory pathogen that can cause severe illness in humans. Therefore it is important to induce a sufficient immune response specific to current strains and to heterosubtypic viruses with vaccines. In this study, we developed a dual-promoter-based bivalent DNA vaccine that encodes both hemagglutinin (HA) and nucleoprotein (NP) proteins from a highly pathogenic A/Chicken/Henan/12/2004 (H5N1) virus. Our results show that the expression levels of HA and NP genes from the dual-promoter plasmid are similar to those seen when they are expressed individually in independent plasmids. When the bivalent DNA vaccine was inoculated via intramuscular injection and in vivo electroporation, high levels of both humoral and cellular immune responses were elicited against homologous H5N1 virus and heterosubtypic H9N2 virus. Furthermore, no obvious antigenic competition was observed between HA and NP proteins in the dual-promoter-based bivalent vaccine compared to monovalent vaccines. Our data suggest that a combination of influenza surface and internal viral genes in a dual-promoter-expressing plasmid may provide a new approach for developing a DNA vaccine that may protect not only specifically against a currently circulating strain, but also may cross-protect broadly against new heterosubtypic viruses.
Definition of human cytomegalovirus-specific target antigens recognized by cytotoxic T cells generated in vitro by using an autologous lymphocyte system. (1986)

We developed an in vitro system for the generation of human cytomegalovirus (CMV)-specific cytotoxic T cells (CTL) that avoids the necessity of constituting a panel of HLA-typed fibroblasts. Autologous donor leucocytes were coated with CMV antigens and were used as both stimulator and target cells. With the use of this system, CMV-specific effector cells were efficiently generated from seropositive but not seronegative donors. These CMV-specific effectors were HLA-restricted and had characteristics of T cells. Maximum lymphoproliferation preceded the appearance of maximum CTL activity by 3 to 4 days, and a close correlation was seen between both activities. Mouse anti-CMV monoclonal antibodies were used in blocking experiments in an attempt to define target antigens recognized by CMV-specific cytotoxic lymphocytes. Monoclonal antibodies directed against an early CMV membrane antigen, against neutralization epitopes, or against nuclear inclusion body protein all specifically inhibited CMV-sensitized effector cell activity but did not affect influenza virus-specific lysis. Monoclonal antibodies directed against a normal cell determinant or against poliovirus did not affect CMV-specific CTL activity. CMV-immune cytotoxic T cells could be consistently and specifically inhibited in their lytic activity by pretreating antigen-coated target cells with monoclonal antibodies directed against CMV-related proteins.
Inhibition of Interleukin-17 Prevents the Development of Arthritis in Vaccinated Mice Challenged withBorrelia burgdorferi (2003)

We showed that Borrelia burgdorferi-vaccinated interferon gamma-deficient (IFN-gamma(0)) mice challenged with the Lyme spirochete developed a prominent chronic severe destructive osteoarthropathy. The immune response underlying the development of the severe destructive arthritis involves interleukin-17 (IL-17). Treatment of vaccinated IFN-gamma(0) mice challenged with B. burgdorferi with anti-IL-17 antibody delayed the onset of swelling of the hind paws but, more importantly, inhibited the development of arthritis. Histopathologic examination confirmed that treatment with anti-IL-17 antibody prevented the destructive arthropathy seen in vaccinated and challenged IFN-gamma(0) mice. Similar preventive results were obtained when vaccinated and challenged IFN-gamma(0) mice were treated with anti-IL-17 receptor antibody or sequentially with anti-IL-17 antibody followed by anti-IL-17 receptor antibody. By contrast, treatment of vaccinated and challenged IFN-gamma(0) mice with recombinant IL-17 (rIL-17) did not alter the development and progression of arthritis found in vaccinated and challenged IFN-gamma(0) mice without treatment with rIL-17. Therapeutic intervention may be a realistic approach to prevent arthritis, especially if IL-17 is involved in the perpetuation of chronic or intermittent arthritis.
Advances in mathematical modeling of hydraulic stimulation of a subterranean fractured reservoir (2005)

Hydraulic stimulation is performed by a high-pressure fluid injection, which leads to a permanent increase in permeability of a volume of rock, typically transforming it from the microdarcy into the millidarcy range. The present paper provides an overview of the recent results in mathematical modeling of this process obtained at Tohoku University, Japan. Several mathematical models are proposed and realized. Within the steady-state approach, the geothermal reservoirs are characterized by parameters measured from field data and the model incorporates the approximations of the fracture mechanical behavior and fluid dynamics in fractured media. Along with the fractal-type distribution of the fracture lengths, the fracture surfaces are also assumed to follow fractal geometry. The latter allows numerical simulation of the natural rock fracture dilation caused by fracture shear offset. Recently, a new simplified non-steady mathematical model of the stimulation process was proposed. This model can be used for assessing the rate of the stimulated volume growth subject to injection pressure and flow rate and for approximate calculation of time required for creating the specified size of the stimulated region.
Direct brain infusion can be enhanced with focused ultrasound and microbubbles (2016)

The delivery of most therapeutic agents is rendered ineffective for the treatment of brain diseases due to the presence of the blood-brain barrier (BBB). The goal of this study was to investigate the effect of pre-infusion focused ultrasound (FUS) and microbubbles on the distribution of direct brain infusion in vivo. A single-element FUS transducer was used in all sonications, which were carried out immediately prior to direct infusion procedures. Mice received direct infusion of either Gadolinium-labeled albumin (Gd-albumin, 74 kDa) or adeno-associated virus (AAV, ∼4 MDa). The volumes of Gd-albumin at 30 min were deemed comparable ( P = 0.334) between the direct infusion (DI)-only group and the FUS + DI group. At 120 min, the FUS + DI group showed significantly higher contrast-enhanced volume (9.76 ± 0.74 mm<sup>3</sup>) than the DI-only group (7.14 ± 0.34 mm<sup>3</sup>). For mice infused with AAV, the total volume of transduction was estimated as GFP-positive regions and FUS + DI group demonstrated significantly higher ( P = 0.017) transduction efficiency in vivo. In conclusion, enhanced bio-distribution of directly infused agents was observed when the targeted region was pre-conditioned with FUS and microbubbles. Focused ultrasound has the potential, as an adjuvant technique, to significantly enhance direct brain infusion and achieve the desired therapeutic outcomes.
Post-packaging frequency tuning of microresonators by pulsed laser deposition (2004)

This paper presents a post-packaging tuning process for microresonators by PLD (pulsed laser deposition). The microresonators are first hermetically packaged using a RTP (rapid thermal processing) aluminum-to-silicon nitride bonding process. The resonator mass is then altered by adding materials on the surface of the structure using PLD to achieve the desired resonant frequency. The demonstrated tuning resolution is 0.5% per laser shot with a laser beam spot size of 25 × 25 µm2 and fluence of 616 mJ cm−2. The laser pulse duration is 6 ns and a 0.35 µm thick gold film is used as the deposition material for comb-drive microresonators resonating at 12.45 kHz.
Modeling the structure of the combining site of an antisweet taste ligand monoclonal antibody NC10.14 (1996)

We report the predicted combining site structure of the monoclonal antibody fragment. NC10.14, which is specific for the superpotent sweetener, N-(p-cyanophenyl-N′-(diphenylmethyl)guanidine acetic acid, using computer-aided molecular modeling and experimental methods, such as fluorescence spectroscopy and circular dichroism. This is the first computer-aided modeling study on a λ-chain antibody fragment. We have also identified the amino acids that are involved in ligand binding. Aromatic residues. L:91(W), L:96(W), and H:100G(Y) are predicted to make van der Waals contacts with the p-cyanophenyl moiety of the ligand. Residue H:56(K) is predicted to provide a counterion for the acetic acid moiety, and H:50(E) provides the negatively charged potential for interaction with the positive guanidinium group. We also make a comparison of the binding site architecture of NC10.14 with that of a related monoclonal antibody fragment NC6.8. © 1996 John Wiley & Sons, Inc.
Polarisation compensated waveguide grating routeron InP (1995)

A novel technique for cancelling polarisation sensitivity in waveguide grating routers on InP is reported. The scheme gives the designer a lot of freedom to choose a particular waveguide structure and does not limit the free spectral range of the router. No performance penalty arises from this polarisation compensation scheme.