gebhart/patrepeval huggingface dataset:
Glycocluster Design for Improved Avidity and Selectivity in Blocking Human Lectin/Plant Toxin Binding to Glycoproteins and Cells (2010)

Blocking lectin/toxin binding to human cells by suitable inhibitors can therapeutically protect them from harmful effects. Clustered design of ligand presentation holds the promise of affinity increase relative to the free sugar and inherent selectivity among lectin targets. Using first a solid-phase assay with a glycoprotein presenting N-glycans as lectin-reactive probe, we assessed the inhibitory potency of bi- to tetravalent clusters on a plant toxin and three human adhesion/growth-regulatory lectins. Enhanced avidity relative to the free sugar was detected together with lectin-type selectivity. These effects were confirmed on the level of cells in vitro, also for two leguminous lectins. The lack of toxicity in cell proliferation assays excluded concerns to further work on these compounds. The given cluster design and the strategic combination of the two assay systems of increasing biorelevance will thus be helpful to take the next steps in drug development, e.g. tailoring the sugar headgroup.
Solidly mounted resonators with carbon nanotube electrodes for biosensing applications (2011)

The work reported here shows a direct experimental comparison of the sensitivities of AlN solidly mounted resonators (SMR)-based biosensors fabricated with standard metal electrodes and with carbon nanotube electrodes. SMRs resonating at frequencies around 1.75 GHz have been fabricated, some devices using a thin film of multi-wall carbon nanotubes (CNTs) as the top electrode material and some identical devices using a chromium/gold electrode. Protein solutions with different concentrations were loaded on the top of the resonators and their responses to mass-load from physically adsorbed coatings were investigated. Results show that resonators using CNTs as the top electrode material exhibited higher frequency change for a given load due to the higher active surface area of a thin film of interconnecting CNTs compared to that of a metal thin film electrode and hence exhibited greater mass loading sensitivity. It is therefore concluded that the use of CNT electrodes on resonators for their use as gravimetric biosensors is viable and worthwhile.
An Homotopy Algorithm for the Lasso with Online Observations (2008)

It has been shown that the problem of l1-penalized least-square regression commonly referred to as the Lasso or Basis Pursuit DeNoising leads to solutions that are sparse and therefore achieves model selection. We propose in this paper RecLasso, an algorithm to solve the Lasso with online (sequential) observations. We introduce an optimization problem that allows us to compute an homotopy from the current solution to the solution after observing a new data point. We compare our method to Lars and Coordinate Descent, and present an application to compressive sensing with sequential observations. Our approach can easily be extended to compute an homotopy from the current solution to the solution that corresponds to removing a data point, which leads to an efficient algorithm for leave-one-out cross-validation. We also propose an algorithm to automatically update the regularization parameter after observing a new data point.
CX3CL1/CX3CR1 regulates nerve injury‐induced pain hypersensitivity through the ERK5 signaling pathway (2013)

Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. The knockdown of ERK5 by intrathecal injection of antisense oligonucleotides suppressed the hyperalgesia and nuclear impact of nuclear factor-κB induced by SNL. The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.
5' upstream sequence and genomic structure of the human primary response gene, EGR-1/TIS8. (1991)

EGR-1/TIS8 is a primary response gene that encodes a zinc finger containing protein and is induced in a number of cell types by a variety of ligands. We have isolated and mapped the human EGR-1/TIS8 gene and sequenced the 5' upstream flanking region. A 'TATA' homology and several putative regulatory elements, including two Sp1 sites, five serum response-like elements, two cAMP response-like elements, an EGR-1 binding site (EBS), and a tetra-decanoyl phorbol acetate (TPA)-responsive element have been identified within 700 nucleotides of the upstream region. We demonstrated that a 500-base pair fragment, which includes several of these possible regulatory sequences, is functional and responsive to TPA in transient transfection assays. A further understanding of the regulation and function of human EGR-1/TIS8 gene expression may provide insight into the mechanisms that control normal and neoplastic proliferation of human cells.
Mechanism of Thy-1-mediated T cell activation: roles of Fc receptors, T200, Ia, and H-2 glycoproteins in accessory cell function. (1981)

Abstract The activation ligand and the molecular and cellular requirements for accessory cell function in murine T cell activation initiated by rabbit anti-Thy-1 antibodies were examined. Both rabbit anti-mouse brain (RaMB) and anti-Thy-1 glycoprotein antibodies initiated T lymphocyte proliferation and precipitated a unique 25,000-dalton glycoprotein after absorption with S49 Thy-1− but not with S49 Thy-1+ T lymphoma cell lines, suggesting that the Thy-1 glycoprotein shares at least a portion of the activation determinant. Antibodies directed against the allodeterminants (Thy-1.1, 1.2) were neither mitogenic or inhibitory to rabbit anti-Thy-1-induced responses. Since rat Thy-1-bearing tissue was effective in absorbing mitogenic activity, it was concluded that the activation ligand was composed of at least 1 rat-mouse shared determinant and possibly an additional mouse-specific determinant(s). The accessory cell requirement was examined by comparing the ability of a number of cell populations to provide helper activity when added to cultures of purified lymph node T lymphocytes pretreated with RaMB. With the exception of peritoneal macrophages, a variety of Fc receptor-(FcR) positive cell types supplied accessory cell function, including B cells, T cells, and macrophages. Helper cell effects were abrogated by UV or glutaralde-hyde treatment, suggesting a requirement for membrane mobility. Accessory cells were not required if aggregation of the RaMB-Thy-1 complex was initiated by anti-lg cross-linking in the absence of helper cells. The hypothesis that the co-redistribution of the FcR-anti-Thy-1 complex involves other membrane proteins in the plasma membrane was tested using monoclonal antibodies directed against H-2, la, and T200 glycoproteins. Anti-H-2K and anti-H-2D, anti-T200, and anti-la antibodies inhibited activation of spleen cells by RaMB but did not affect Con A-, PHA-, or LPS-induced proliferative responses. Antibody pretreatment and genetic evidence strongly favored the conclusion that inhibition by anti-H-2 and anti-T200 antibodies was directed through the accessory cell rather than the responding T cell. It is postulated that transmembrane mobility of these components and/or the FcR on the accessory cell is in some way compromised by these antibodies.
Induction of tumor necrosis factor production from monocytes stimulated with mannuronic acid polymers and involvement of lipopolysaccharide-binding protein, CD14, and bactericidal/permeability-increasing factor (1997)

Well-defined polysaccharides, such as beta1-4-linked D-mannuronic acid (poly[M]) derived from Pseudomonas aeruginosa, induce monocytes to produce tumor necrosis factor (TNF) through a pathway involving membrane CD14. In this study we have investigated the effects of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing factor (BPI) on poly(M) binding to monocytes and induction of TNF production. We show that LBP increased the TNF production from monocytes stimulated with poly(M). Addition of sCD14 alone had only minor effects, but when it was added together with LBP, a rise in TNF production was seen. BPI was found to inhibit TNF production from monocytes stimulated with poly(M) in the presence of LBP, LBP-sCD14, or 10% human serum. Binding studies showed that poly(M) bound to LBP- and BPI-coated immunowells, while no significant binding of poly(M) to sCD14-coated wells in the absence of serum was observed. Binding of poly(M) to monocytes was also examined by flow cytometry, and it was shown that the addition of LBP or 10% human serum clearly increased the binding of poly(M) to monocytes. BPI inhibited the binding of poly(M) to monocytes in the presence of LBP, LBP-sCD14, or 10% human serum. Our data demonstrate a role for LBP, LBP-sCD14, and BPI in modulating TNF responses of defined polysaccharides.
ChemInform Abstract: Scandium, Yttrium, the Lanthanoids and the Actinoids (1988)

Abstract Review: (178 refs.
Combining Single and Packet-Ray Tracing for Arbitrary Ray Distributions on the Intel MIC Architecture (2011)

Wide-SIMD hardware is power and area efficient, but it is challenging to efficiently map ray tracing algorithms to such hardware especially when the rays are incoherent. The two most commonly used schemes are either packet tracing, or relying on a separate traversal stack for each SIMD lane. Both work great for coherent rays, but suffer when rays are incoherent: The former experiences a dramatic loss of SIMD utilization once rays diverge; the latter requires a large local storage, and generates multiple incoherent streams of memory accesses that present challenges for the memory system. In this paper, we introduce a single-ray tracing scheme for incoherent rays that uses just one traversal stack on 16-wide SIMD hardware. It uses a bounding-volume hierarchy with a branching factor of four as the acceleration structure, exploits four-wide SIMD in each box and primitive intersection test, and uses 16-wide SIMD by always performing four such node or primitive tests in parallel. We then extend this scheme to a hybrid tracing scheme that automatically adapts to varying ray coherence by starting out with a 16-wide packet scheme and switching to the new single-ray scheme as soon as rays diverge. We show that on the Intel Many Integrated Core architecture this hybrid scheme consistently, and over a wide range of scenes and ray distributions, outperforms both packet and single-ray tracing.
Telecommunication applications over the low voltage power distribution grid (2002)

Using low voltage energy distribution grids as high-speed communication networks opens up the possibility to utilities to establish widespread local area networks for telecommunication services such as telephony and Internet access without the necessity of additional cabling. Since communication systems, suitable for high-speed transmission over electrical power lines, are not available yet, considerable efforts are currently being spent on designing such systems. Due to the special properties of power distribution grids as communication channels, profound investigations of the channel properties must have been done before a successful development of reliable and efficient systems is possible. At the University of Karlsruhe extensive measurements of typical channel properties are currently under way. Some of the results are presented in this work, giving a first impression of the most important channel properties. However, the main goal of this paper is to investigate and describe suitable strategies for advanced multiple access systems.
Antibody Glycosylation (2009)

This chapter contains sections titled: Introduction Antibodies Glycosylation IgG-Fc Effector Functions Individual IgG-Fc Glycoforms IgG-Fab Glycosylation Recombinant Monoclonal Antibodies for Therapy Conclusions and Future Perspectives References
Nanofibrous Scaffolds Incorporating PDGF-BB Microspheres Induce Chemokine Expression and Tissue Neogenesis In Vivo (2008)

Platelet-derived growth factor (PDGF) exerts multiple cellular effects that stimulate wound repair in multiple tissues. However, a major obstacle for its successful clinical application is the delivery system, which ultimately controls the in vivo release rate of PDGF. Polylactic-co-glycolic acid (PLGA) microspheres (MS) in nanofibrous scaffolds (NFS) have been shown to control the release of rhPDGF-BB in vitro. In order to investigate the effects of rhPDGF-BB release from MS in NFS on gene expression and enhancement of soft tissue engineering, rhPDGF-BB was incorporated into differing molecular weight (MW) polymeric MS. By controlling the MW of the MS over a range of 6.5 KDa-64 KDa, release rates of PDGF can be regulated over periods of weeks to months in vitro. The NFS-MS scaffolds were divided into multiple groups based on MS release characteristics and PDGF concentration ranging from 2.5-25.0 microg and evaluated in vivo in a soft tissue wound repair model in the dorsa of rats. At 3, 7, 14 and 21 days post-implantation, the scaffold implants were harvested followed by assessments of cell penetration, vasculogenesis and tissue neogenesis. Gene expression profiles using cDNA microarrays were performed on the PDGF-releasing NFS. The percentage of tissue invasion into MS-containing NFS at 7 days was higher in the PDGF groups when compared to controls. Blood vessel number in the HMW groups containing either 2.5 or 25 microg PDGF was increased above those of other groups at 7d (p<0.01). Results from cDNA array showed that PDGF strongly enhanced in vivo gene expression of the CXC chemokine family members such as CXCL1, CXCL2 and CXCL5. Thus, sustained release of rhPDGF-BB, controlled by slow-releasing MS associated with the NFS delivery system, enhanced cell migration and angiogenesis in vivo, and may be related to an induced expression of chemokine-related genes. This approach offers a technology to accurately control growth factor release to promote soft tissue engineering in vivo.
Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes (2006)

Anaplastic large cell lymphomas (ALCLs) represent a subset of lymphomas in which the anaplastic lymphoma kinase (ALK) gene is frequently fused to the nucleophosmin (NPM) gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo and that ALK activity is strictly required for the survival of ALK-positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK-positive ALCL cell lines, abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell-permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBPbeta and the antiapoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK-positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.
Anti‐VEGF‐A therapy reduces lymphatic vessel density and expression of VEGFR‐3 in an orthotopic breast tumor model (2007)

Because metastasis contributes significantly to cancer mortality, understanding its mechanisms is crucial to developing effective therapy. Metastasis is facilitated by lymphangiogenesis, the growth of new intratumoral or peritumoral lymphatic vessels from pre-existing vessels. Vascular endothelial growth factor A (VEGF-A) is a well-known angiogenic factor. Increasing evidence implicates VEGF-A in lymphangiogenesis, although the mechanism of its pro-lymphangiogenic effect is poorly understood. We examined the effect of the anti-VEGF-A neutralizing antibody 2C3 on tumor lymphangiogenesis and metastasis in an orthotopic breast carcinoma model using MDA-MB-231 cells and its luciferase-tagged derivative, 231-Luc(+) cells. Anti-VEGF-A antibody therapy reduced blood and lymphatic vessel densities by 70% and 80%, respectively, compared with the control antibody. Treatment with 2C3 antibody also decreased incidence of lymphatic and pulmonary metastases by 3.2- and 4.5-fold, respectively. Macrophage infiltration was reduced in 2C3-treated tumors by 32%, but VEGF-C expression was unchanged. In contrast, neoplastic cells and blood vessels in tumors from 2C3-treated mice expressed significantly less angiopoietin-2 (Ang-2) than tumors from control mice. The reduction in Ang-2 was associated with inhibition of VEGFR-3 expression in intratumoral lymphatic endothelial cells. Both VEGF-A and Ang-2 upregulated the expression of VEGFR-3 in cultured lymphatic endothelial cells. VEGF-A induced proliferation of lymphatic endothelial cells was reduced by 50% by soluble Tie-2, suggesting that Ang-2 is an intermediary of the pro-lymphangiogenic VEGF-A effect. These results suggest a novel mechanism by which anti-VEGF-A therapy may suppress tumor lymphangiogenesis and subsequent metastasis supporting the use of anti-VEGF-A therapy to control metastasis clinically.
PRO- AND ANTI-CANCER EFFECTS OF IMMUNOSUPPRESSIVE AGENTS USED IN ORGAN TRANSPLANTATION (2004)

Development of cancer is a feared, and increasingly apparent, complication of long-term immunosuppressive therapy in transplant recipients. In addition to the need to reduce cancer occurrence in these patients, therapeutic protocols are lacking to simultaneously attack the malignancy and protect the allograft when neoplasms do occur. In this overview, we present the current literature regarding the pro- and anti-neoplastic effects of immunosuppressive agents on cancer growth and development. Recent experimental findings are paving the way for new therapeutic strategies aimed at both protecting an allograft from immunologic rejection and addressing the problem of cancer in this high-risk population.
A DVB-S2 compliant LDPC decoder integrating the Horizontal Shuffle Scheduling (2006)

Low-density parity check codes (LDPC) are a class of channel decoding codes used in digital communications. Very high error correcting performances can be reached with such codes but they require both a great computing effort and randomly constructed decoding matrices. LDPC codes are used to perform the channel coding of the satellite television broadcast standard DVB-S2. This paper proposes a way to design massively parallel hardware architecture of DVB-S2 compliant LDPC decoders. It is based on a particular way to schedule all the algorithm's calculations. The proposed architecture speeds-up the decoding process, allowing the algorithm to converge faster with no significant performance loss. Moreover, a particular data update mechanism has been developed in order to avoid all data conflicts inherent to DVB-S2 matrices even for highly parallel implementations. This paper describes our hardware LDPC decoder architecture and its processing elements. Estimated silicon area of this decoder is 11 mm in ST 90 nm technology and the decoding throughput reaches 591 M bps at 300 MHz for rate 1/2 and code size of 64800
Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding α-N-acetylglucosaminidase (1999)

The Sanfilippo syndrome type B is an autosomal recessive disorder caused by mutation in the gene (NAGLU) encoding alpha-N-acetylglucosaminidase, a lysosomal enzyme required for the stepwise degradation of heparan sulfate. The most serious manifestations are profound mental retardation, intractable behavior problems, and death in the second decade. To generate a model for studies of pathophysiology and of potential therapy, we disrupted exon 6 of Naglu, the homologous mouse gene. Naglu-/- mice were healthy and fertile while young and could survive for 8-12 mo. They were totally deficient in alpha-N-acetylglucosaminidase and had massive accumulation of heparan sulfate in liver and kidney as well as secondary changes in activity of several other lysosomal enzymes in liver and brain and elevation of gangliosides G(M2) and G(M3) in brain. Vacuolation was seen in many cells, including macrophages, epithelial cells, and neurons, and became more prominent with age. Although most vacuoles contained finely granular material characteristic of glycosaminoglycan accumulation, large pleiomorphic inclusions were seen in some neurons and pericytes in the brain. Abnormal hypoactive behavior was manifested by 4.5-mo-old Naglu-/- mice in an open field test; the hyperactivity that is characteristic of affected children was not observed even in younger mice. In a Pavlovian fear conditioning test, the 4.5-mo-old mutant mice showed normal response to context, indicating intact hippocampal-dependent learning, but reduced response to a conditioning tone, perhaps attributable to hearing impairment. The phenotype of the alpha-N-acetylglucosaminidase-deficient mice is sufficiently similar to that of patients with the Sanfilippo syndrome type B to make these mice a good model for study of pathophysiology and for development of therapy.
Effect of process parameters on the surface morphology and mechanical performance of silicon structures after deep reactive ion etching (DRIE) (2002)

The ability to predict and control the influence of process parameters during silicon etching is vital for the success of most MEMS devices. In the case of deep reactive ion etching (DRIE) of silicon substrates, experimental results indicate that etch performance as well as surface morphology and post-etch mechanical behavior have a strong dependence on processing parameters. In order to understand the influence of these parameters, a set of experiments was designed and performed to fully characterize the sensitivity of surface morphology and mechanical behavior of silicon samples produced with different DRIE operating conditions. The designed experiment involved a matrix of 55 silicon wafers with radius hub flexure (RHF) specimens which were etched 10 min under varying DRIE processing conditions. Data collected by interferometry, atomic force microscopy (AFM), profilometry, and scanning electron microscopy (SEM), was used to determine the response of etching performance to operating conditions. The data collected for fracture strength was analyzed and modeled by finite element computation. The data was then fitted to response surfaces to model the dependence of response variables on dry processing conditions.
Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum (2009)

A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established.