gebhart/patrepeval huggingface dataset:
Neuraminidase associated with coliphage E that specifically depolymerizes the Escherichia coli K1 capsular polysaccharide (1985)

Plaque morphology indicated that the five Escherichia coli K1-specific bacteriophages (A to E) described by Gross et al. (R. J. Gross, T. Cheasty, and B. Rowe, J. Clin. Microbiol. 6:548-550, 1977) encode K1 depolymerase activity that is present in both the bound and free forms. The free form of the enzyme from bacteriophage E was purified 238-fold to apparent homogeneity and in a high yield from ammonium sulfate precipitates of cell lysates by a combination of CsCl density gradient ultracentrifugation, gel filtration, and anion-exchange chromatography. The enzyme complex had an apparent molecular weight of 208,000, as judged from its behavior on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and was dissociated by sodium dodecyl sulfate at 100 degrees C to yield two polypeptides with apparent molecular weights of 74,000 and 38,500. Optimum hydrolytic activity was observed at pH 5.5, and activity was strongly inhibited by Ca2+; the Km was 7.41 X 10(-3) M. Rapid hydrolysis of both the O-acetylated and non-O-acetylated forms of the K1 antigen, an alpha 2----8-linked homopolymer of N-acetylneuraminic acid, and of the meningococcus B antigen was observed. Limited hydrolysis of the E. coli K92 antigen, an N-acetylneuraminic acid homopolymer containing alternating alpha 2----8 and alpha 2----9 linkages, occurred, but the enzyme failed to release alpha 2----3-, alpha 2----6-, or alpha 2----9-linked sialic residues from a variety of other substrates.
Protein Kinase Inhibitor-(6-22)-amide Peptide Analogs with Standard and Nonstandard Amino Acid Substitutions for Phenylalanine 10 (1989)

The minimal structure in the heat-stable inhibitor protein of cAMP-dependent protein kinase required for a low nanomolar potency of inhibition is the peptide Thr6-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-+ ++Ile22-NH2 (PKI-(6-22)-amide). While primary structural determinants for interaction with the protein kinase are distributed throughout the 17 residues of this peptide, we have previously shown that phenylalanine 10 in the NH2-terminal portion is a particularly important determinant for high affinity binding (Glass, D. B., Cheng, H.-C., Mende-Mueller, L., Reed, J., and Walsh, D. A. (1989) J. Biol. Chem. 264, 8802-8810). To investigate this requirement further, peptide analogs of PKI-(6-22)-amide in which various natural and nonstandard amino acids are substituted for phenylalanine 10 have been synthesized and tested for inhibitory potency against the catalytic subunit of the protein kinase. Consistent with the importance of the hydrophobicity of phenylalanine, an alanine 10 substitution analog exhibited a 270-fold decrease in inhibitory potency, whereas the leucine 10 analog lost only 33-fold in activity as compared to the parent peptide PKI-(6-22)-amide. Peptides containing the spatial conformation analogs D-phenylalanine, homophenylalanine, or phenylglycine were 60-120-fold less potent than the parent peptide. Peptides containing various para-substituted phenylalanines at position 10 were only 5-11-fold less potent. One exception to this was (4'-azidophenylalanine 10)PKI-(6-22)-amide, which was nearly equipotent with the parent inhibitor. The most potent analogs were those peptides containing highly aromatic residues at position 10. The 2'-thienylalanine 10, tryptophan (formyl) 10, tryptophan 10, and the 1'-naphthylalanine 10 analogs were 3-fold less potent, equipotent, slightly more potent, and 4-fold more potent than the parent peptide inhibitor, respectively. We conclude that phenylalanine 10 in PKI-(6-22)-amide, and presumably in the native protein inhibitor, interacts through specific hydrophobic and/or aromatic binding to a hydrophobic pocket or cleft near the active site of the protein kinase.
Pyrazolo[3,4‐d]pyrimidines Containing an Extended 3‐Substituent as Potent Inhibitors of Lck — A Selectivity Insight. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
Development of a Highly Active Nanoliposomal Irinotecan Using a Novel Intraliposomal Stabilization Strategy (2006)

Liposome formulations of camptothecins have been actively pursued because of the potential for significant pharmacologic advantages from successful drug delivery of this important class of anticancer drugs. We describe nanoliposomal CPT-11, a novel nanoparticle/liposome construct containing CPT-11 (irinotecan) with unprecedented drug loading efficiency and in vivo drug retention. Using a modified gradient loading method featuring a sterically hindered amine with highly charged, multivalent anionic trapping agents, either polymeric (polyphosphate) or nonpolymeric (sucrose octasulfate), liposomes were capable of entrapping CPT-11 at extremely high drug-to-lipid ratios (>800 g CPT-11/mol phospholipid) and retaining encapsulated drug in vivo with a half-life of drug release in the circulation of 56.8 hours. CPT-11 was also protected from hydrolysis to the inactive carboxylate form and from metabolic conversion to SN-38 while circulating. The maximum tolerated dose in normal mice was determined to be 80 mg/kg for free CPT-11 and >320 mg/kg for nanoliposomal CPT-11. Nanoliposomal CPT-11 showed markedly superior efficacy when compared with free CPT-11 in human breast (BT474) and colon (HT29) cancer xenograft models. This study shows that intraliposomal stabilization of CPT-11 using a polymeric or highly charged, nonpolymeric polyanionic trapping agent results in a markedly active antitumor agent with low toxicity.
Multi-directional geodesic neural networks via equivariant convolution (2018)

We propose a novel approach for performing convolution of signals on curved surfaces and show its utility in a variety of geometric deep learning applications. Key to our construction is the notion of directional functions defined on the surface, which extend the classic real-valued signals and which can be naturally convolved with with real-valued template functions. As a result, rather than trying to fix a canonical orientation or only keeping the maximal response across all alignments of a 2D template at every point of the surface, as done in previous works, we show how information across all rotations can be kept across different layers of the neural network. Our construction, which we call multi-directional geodesic convolution , or directional convolution for short, allows, in particular, to propagate and relate directional information across layers and thus different regions on the shape. We first define directional convolution in the continuous setting, prove its key properties and then show how it can be implemented in practice, for shapes represented as triangle meshes. We evaluate directional convolution in a wide variety of learning scenarios ranging from classification of signals on surfaces, to shape segmentation and shape matching, where we show a significant improvement over several baselines.
Large-scale 3D imaging of insects with natural color (2019)

High-resolution 3D imaging technology has found a number of applications in many biological fields. However, the existing 3D imaging tools are often too time-consuming to use on large-scale specimens, such as centimeter-sized insects. In addition, most 3D imaging systems discard the natural color information of the specimens. To surmount these limitations, we present a structured illumination-based approach capable of delivering large field-of-view three-dimensional images. With this approach, 580nm lateral resolution full-color 3D images and 3D morphological data in the size range of typical insect samples can be obtained. This method provides a promising approach that can be used to support many different types of entomological investigations, including taxonomy, evolution, bionics, developmental biology, functional morphology, paleontology, forestry, etc.
Materials for Bioresorbable Radio Frequency Electronics (2013)

Materials, device designs and manufacturing approaches are presented for classes of RF electronic components that are capable of complete dissolution in water or biofluids. All individual passive/active components as well as system-level examples such as wireless RF energy harvesting circuits exploit active materials that are biocompatible. The results provide diverse building blocks for physically transient forms of electronics, of particular potential value in bioresorbable medical implants with wireless power transmission and communication capabilities.
Enzyme replacement therapy for Gaucher's disease in patient treated for non-small cell lung cancer. (2009)

Gaucher's disease (GD) is an autosomal recessive lysosomal storage disease resulting in an abnormal accumulation of glucocerebrosides in macrophages. Recent studies have reported that patients with GD are at an increased risk of developing malignancies. Here, a rare case of a patient with Type I GD who developed adenocarcinoma of the lung that was treated with chemotherapy, radiotherapy and biological agents inhibiting receptor tyrosine kinases is presented. The patient developed unusually severe hematological toxicity to chemotherapy as compared to nonsmall cell lung cancer patients without the GD defect. Pancytopenia is already present in GD patients and it is reasonable to expect an increased risk of hematological toxicity in treating solid tumors in these patients. Therefore, it is advisable to consider early glucocerebrosidase replacement therapy in GD patients receiving cytotoxic or targeted therapy for cancer.
Total active area silicon photodiode array (1969)

A novel approach is described for fabricating high resolution silicon photodiode arrays whereby virtually none of the irradiated array area is lost for interelement isolation or lead contacting requirements. Element isolation is achieved by biasing a p-v-n diode so that the depletion layer reaches a pattern of grooves etched into the side opposite the radiation. Experiments illustrating the concept feasibility on a two element array are presented as well as preliminary results on a 7×7 array having elements on centers separated by 0.013 cm.
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance (2002)

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of alphaDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with alphaDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic alphaCD40 antibody produced large amounts of interleukin 2 and interferon gamma, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
The Lin12-Notch Repeats of Pregnancy-associated Plasma Protein-A Bind Calcium and Determine Its Proteolytic Specificity (2004)

The Lin12-Notch repeat (LNR) module of about 35 residues is a hallmark of the Notch receptor family. Three copies, arranged in tandem, are invariably present in the extracellular portion of the Notch receptors. Although their function is unknown, genetic and biochemical data indicate that the LNR modules participate in the regulation of ligand-induced proteolytic cleavage of the Notch receptor, a prerequisite to intramembrane cleavage and Notch signaling. Outside the Notch receptor family, the LNR module is present only in the metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) and its homologue PAPP-A2, which also contain three copies. Curiously, LNR modules 1 and 2 are present within the proteolytic domain of PAPP-A/A2, but LNR3 is separated from LNR2 by more than 1000 amino acids. The growth factor antagonists insulin-like growth factor-binding protein (IGFBP)-4 and -5 are both substrates of PAPP-A. We provide here evidence that the PAPP-A LNR modules function together to determine the proteolytic specificity of PAPP-A. Analysis of C-terminally truncated PAPP-A mutants followed by the analysis of LNR deletion mutants demonstrated that each of the three PAPP-A LNR modules is strictly required for proteolytic activity against IGFBP-4 but not for proteolytic activity against IGFBP-5. Individual substitution of conserved LNR residues predicted to participate in calcium coordination caused elimination (D341A, D356A, D389A, D1484A, D1499A, and D1502A) or a significant reduction (D359A and E392A) of IGFBP-4 proteolysis, whereas IGFBP-5 proteolysis was unaffected. The activity of the latter mutants against IGFBP-4 could be partially rescued by calcium, and the addition of the calcium-binding protein calbindin D9k to wild-type PAPP-A eliminated activity against IGFBP-4 but not against IGFBP-5, demonstrating that the PAPP-A LNR modules bind calcium ions. We propose a model in which LNR3 is spatially localized in proximity to LNR1 and -2, forming a single functional unit.
Fullerenes as precursors for diamond film growth without hydrogen or oxygen additions (1994)

Diamond films are predominantly grown using approximately 1% of a hydrocarbon precursor in hydrogen gas. Hydrogen is generally believed to be necessary for the diamond thin-film growth process. However, hydrogen in varying amounts is inevitably incorporated in the growing diamond lattice, leading to structural defects. We report here the successful growth of diamond films using fullerene precursors in an argon microwave plasma, a unique development achieved without the addition of hydrogen or oxygen. We speculate that collisional fragmentation of C60 to give C2 could be responsible for the high growth rate of the very-fine-grained diamond films.
Efficient Inference in Fully Connected CRFs with Gaussian Edge Potentials (2012)

Most state-of-the-art techniques for multi-class image segmentation and labeling use conditional random fields defined over pixels or image regions. While region-level models often feature dense pairwise connectivity, pixel-level models are considerably larger and have only permitted sparse graph structures. In this paper, we consider fully connected CRF models defined on the complete set of pixels in an image. The resulting graphs have billions of edges, making traditional inference algorithms impractical. Our main contribution is a highly efficient approximate inference algorithm for fully connected CRF models in which the pairwise edge potentials are defined by a linear combination of Gaussian kernels. Our experiments demonstrate that dense connectivity at the pixel level substantially improves segmentation and labeling accuracy.
Data mining: an industrial research perspective (1997)

Just what exactly is data mining? At a broad level, it is the process by which accurate and previously unknown information is extracted from large volumes of data. This information should be in a form that can be understood, acted upon, and used for improving decision processes. Obviously, with this definition, data mining encompasses a broad set of technologies, including data warehousing, database management, data analysis algorithms, and visualization. The crux of the appeal for this new technology lies in the data analysis algorithms, since they provide automated mechanisms for sifting through data and extracting useful information. The analysis capability of these algorithms, coupled with today's data warehousing and database management technology, make corporate and industrial data mining possible. The data representation model for such algorithms is quite straightforward. Data is considered to be a collection of records, where each record is a collection of fields. Using this tabular data model, data mining algorithms are designed to operate on the contents, under differing assumptions, and delivering results in differing formats. The data analysis algorithms (or data mining algorithms, as they are more popularly known nowadays) can be divided into three major categories based on the nature of their information extraction: predictive modeling (also called classification or supervised learning), clustering (also called segmentation or unsupervised learning), and frequent pattern extraction.
Calcium Phosphate Nanoparticles Induce Mucosal Immunity and Protection against Herpes Simplex Virus Type 2 (2002)

Previously we reported that calcium phosphate nanoparticles (CAP) represented a superior alternative to alum adjuvants in mice immunized with viral protein. Additionally, we showed that CAP was safe and elicited no detectable immunoglobulin E (IgE) response. In this study, we demonstrated that following mucosal delivery of herpes simplex virus type 2 (HSV-2) antigen with CAP, CAP adjuvant enhanced protective systemic and mucosal immunity versus live virus. Mice were immunized intravaginally and intranasally with HSV-2 protein plus CAP adjuvant (HSV-2+CAP), CAP alone, phosphate-buffered saline, or HSV-2 alone. HSV-2+CAP induced HSV-specific mucosal IgA and IgG and concurrently enhanced systemic IgG responses. Our results demonstrate the potency of CAP as a mucosal adjuvant. Furthermore, we show that systemic immunity could be induced via the mucosal route following inoculation with CAP-based vaccine. Moreover, neutralizing antibodies were found in the sera of mice immunized intranasally or intravaginally with HSV-2+CAP. Also, the results of our in vivo experiments indicated that mice vaccinated with HSV-2+CAP were protected against live HSV-2 infection. In conclusion, these preclinical data support the hypothesis that CAP may be an effective mucosal adjuvant that protects against viral infection.
Induction of CD8+ T cells using heterologous prime‐boost immunisation strategies (1999)

One of the current challenges in vaccine design is the development of antigen delivery systems or vaccination strategies that induce high protective levels of CD8+ T cells. These cells are crucial for protection against certain tumours and intracellular pathogens such as the liver-stage parasite of malaria. A liver-stage malaria vaccine should therefore include CD8+ T-cell-inducing components. This review provides an overview of prime-boost immunisation strategies that result in protective CD8+ T-cell responses against malaria with an emphasis on work from our laboratory. Possible mechanisms explaining why heterologous prime-boost strategies, in particular boosting with replication-impaired recombinant poxviruses, are so effective are discussed.
The contrasting IgG-binding interactions of human and herpes simplex virus Fc receptors (2002)

A virally encoded, high-affinity Fc receptor (FcR) is found on herpes simplex virus type 1 (HSV-1) particles and infected cells where its binding of non-immune IgG protects cells from host-mediated lysis. Whilst mutation or aglycosylation of the IgG CH2 domain reduced binding to human FcR, the interaction with HSV-1 FcR was not affected. However, the HSV-1 FcR, unlike human FcR, discriminates between human IgG1 allotypes, being sensitive to changes at positions 214 (CH1) and 356/358 (CH3), away from its proposed binding site at the CH2-CH3 interface. The biological consequences are not known but this is the first evidence of a major functional difference between IgG1 allotypes.
Producing Recombinant Adeno-Associated Virus in Foster Cells: Overcoming Production Limitations Using a Baculovirus–Insect Cell Expression Strategy (2009)

Establishing pharmacological parameters, such as efficacy, routes of administration, and toxicity, for recombinant adeno-associated virus (rAAV) vectors is a prerequisite for gaining acceptance for clinical applications. In fact, even a therapeutic window, that is, the dose range between therapeutic efficacy and toxicity, has yet to be determined for rAAV in vivo. Multiphase clinical trials investigating the safety and efficacy of recombinant AAV-based therapeutics will require unprecedented vector production capacity to meet the needs of preclinical toxicology studies, and the progressive clinical protocol phases of safety/dose escalation (phase I), efficacy (phase II), and high-enrollment, multicenter evaluations (phase III). Methods of rAAV production capable of supporting such trials must be scalable, robust, and efficient. We have taken advantage of the ease of scalability of nonadherent cell culture techniques coupled with the inherent efficiency of viral infection to develop an rAAV production method based on recombinant baculovirus-mediated expression of AAV components in insect-derived suspension cells.
Enhancement of mRNA in situ hybridization signal by microwave heating. (1995)

The enhancing effect of the hybridization signal obtained using MW allows shorter autoradiographic exposure times and/or the use of lower concentrations of radioactive probes for the detection of mRNA or the detection of mRNA expressed at the threshold of detection with usual protocols.
Locally dividing macrophages in normal and inflamed mammary glands. (1986)

Goat mammary macrophage division in vivo was assessed by detection of mitotic figures, by autoradiographic measurement of the uptake of 3H thymidine, and by a 96-well proliferation assay. Autoradiography revealed that 3.74 +/- 0.77% of nonstimulated mammary macrophages were actively synthesizing DNA. Eight days of sterile inflammation, induced by lipopolysaccharide or thioglycollate, increased mammary macrophage division (10.9 +/- 2.1%). The division increased within 2 h after inducing inflammation with thioglycollate. After 1 day, the rate of division decreased, and another increase occurred 3-4 days later. The high rate of division was maintained for greater than 60 days after the induction of sterile inflammation. Division was further shown to occur by injecting 3H-thymidine directly into the mammary gland, harvesting the macrophages 1.5 h later, and determining incorporation by autoradiography. The results of all assays of division were in agreement, suggesting they reflected the same event. The dividing cells were nonspecific esterase-positive, adherent, motile, phagocytic, and had morphological characteristics of macrophages.