gebhart/patrepeval huggingface dataset:
Neutralization Efficiency Is Greatly Enhanced by Bivalent Binding of an Antibody to Epitopes in the V4 Region and the Membrane-Proximal External Region within One Trimer of Human Immunodeficiency Virus Type 1 Glycoproteins (2010)

Most antibodies are multivalent, with the potential to bind with high avidity. However, neutralizing antibodies commonly bind to virions monovalently. Bivalent binding of a monoclonal antibody (MAb) to a virion has been documented only in a single case. Thus, the role of high avidity in antibody-mediated neutralization of viruses has not been defined clearly. In this study, we demonstrated that when an artificial 2F5 epitope was inserted in the gp120 V4 region so that an HIV-1 envelope glycoprotein (Env) trimer contains a natural 2F5 epitope in the gp41 membrane-proximal envelope region (MPER) and an artificially engineered 2F5 epitope in the gp120 V4 region, bivalent 2F5 IgG achieved greatly enhanced neutralization efficiency, with a 50% inhibitory concentration (IC(50)) decrease over a 2-log scale. In contrast, the monovalent 2F5 Fab fragment did not exhibit any appreciable change in neutralization efficiency in the same context. These results demonstrate that bivalent binding of 2F5 IgG to a single HIV-1 Env trimer results in dramatic enhancement of neutralization, probably through an increase in binding avidity. Furthermore, we demonstrated that bivalent binding of MAb 2F5 to the V4 region and MPER of an HIV-1 Env trimer can be achieved only in a specific configuration, providing an important insight into the structure of a native/infectious HIV-1 Env trimer. This specific binding configuration also establishes a useful standard that can be applied to evaluate the biological relevance of structural information on the HIV-1 Env trimer.
Involvement of Panton-Valentine Leukocidin--Producing Staphylococcus aureus in Primary Skin Infections and Pneumonia (1999)

Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and tissue necrosis. It is produced by fewer than 5% of Staphylococcus aureus strains. A collection of 172 S. aureus strains were screened for PVL genes by polymerase chain reaction amplification. PVL genes were detected in 93% of strains associated with furunculosis and in 85% of those associated with severe necrotic hemorrhagic pneumonia (all community-acquired). They were detected in 55% of cellulitis strains, 50% of cutaneous abscess strains, 23% of osteomyelitis strains, and 13% of finger-pulp-infection strains. PVL genes were not detected in strains responsible for other infections, such as infective endocarditis, mediastinitis, hospital-acquired pneumonia, urinary tract infection, and enterocolitis, or in those associated with toxic-shock syndrome. It thus appears that PVL is mainly associated with necrotic lesions involving the skin or mucosa.
National Treasurer's Report (1992)

The national treasurer reports on ASME's financial position and outlines the various tasks undertaken during the year.
A single vector containing modified cre recombinase and LOX recombination sequences for inducible tissue-specific amplification of gene expression (2001)

The selective alteration of the genome using Cre recombinase to target the rearrangement of genes flanked by LOX recognition sequences has required the use of two separate genetic constructs in trans, one containing cre and the other containing the gene of interest flanked by LOX sites. We have developed a strategy in which both the cre recombinase gene and LOX recombination sites may be cloned within a single vector in cis. This method uses a modified form of Cre (CREM) that contains alterations to the 5 region including the introduction of a Kozak consensus sequence and insertion of a functional intron. This system allows for the inducible, tissuespecific activation or inactivation of gene expression in a single vector and can be utilized for the 300-fold amplification of gene expression from a weak promoter. This approach can be applied to targeting strategies for generating genetically altered mice and gene therapy.
Low- versus high-dose radioimmunotherapy with humanized anti-CD22 or chimeric anti-CD20 antibodies in a broad spectrum of B cell-associated malignancies. (1999)

Both CD22 and CD20 have been used successfully as target molecules for radioimmunotherapy (RAIT) of low-grade B cell non-Hodgkin's lymphoma. Because both CD20 and CD22 are highly expressed relatively early in the course of B cell maturation, and because its expression is maintained up to relatively mature stages, we studied the potential of the humanized anti-CD22 antibody, hLL2, as well as of the chimeric anti-CD20 (chCD20) antibody, rituximab (IDEC-C2B8), for low- or high-dose (myeloablative) RAIT of a broad range of B cell-associated hematological malignancies. A total of 10 patients with chemorefractory malignant neoplasms of B cell origin were studied with diagnostic (n = 5) and/or potentially therapeutic doses (n = 9) of hLL2 (n = 4; 0.5 mg/kg, 8-315 mCi of 131I) or chCD20 (n = 5; 2.5 mg/kg, 15-495 mCi of 131I). The diagnostic doses were given to establish the patients' eligibility for RAIT and to estimate the individual radiation dosimetry. One patient suffered of Waldenström's macroglobulinemia, eight patients had low- (n = 4), intermediate- (n = 2) or high- (n = 2) grade non-Hodgkin's lymphoma, and one patient had a chemorefractory acute lymphatic leukemia, after having failed five heterologous bone marrow or stem cell transplantations. Three of these 10 patients were scheduled for treatment with conventional (30-63 mCi, cumulated doses of up to 90 mCi of 131I) and 7 with potentially myeloablative (225-495 mCi of 131I) activities of 131I-labeled hLL2 or chCD20 (0.5 and 2.5 mg/kg, respectively); homologous (n = 6) or heterologous (n = 1) stem cell support was provided in these cases. Good tumor targeting was observed in all diagnostic as well as posttherapeutic scans of all patients. In myeloablative therapies, the therapeutic activities were calculated based on the diagnostic radiation dosimetry, aiming at lung and kidney doses < or = 20 Gy. Stem cells were reinfused when the whole-body activity retention fell below 20 mCi. In eight assessable patients, five had complete remissions, two experienced partial remissions (corresponding to an overall response rate of 87%), and one (low-dose) patient had progressive disease despite therapy. In the five assessable, actually stem-cell grafted patients, the complete response rate was 100%. Both CD20 and CD22 seem to be suitable target molecules for high-dose RAIT in a broad spectrum of hematological malignancies of B cell origin with a broad range of maturation stages (from acute lymphatic leukemia to Waldenström's macroglobulinemia). The better therapeutic outcome of patients undergoing high-dose, myeloablative RAIT favors this treatment concept over conventional, low-dose regimens.
Elucidation of IgH intronic enhancer functions via germ-line deletion (2005)

Studies of chimeric mice demonstrated that the core Ig heavy chain (IgH) intronic enhancer (iEmu) functions in V(D)J and class switch recombination at the IgH locus. To more fully evaluate the role of this element in these and other processes, we generated mice homozygous for germ-line mutations in which the core sequences of iEmu (cEmu) were either deleted (cEmu(Delta/Delta) mice) or replaced with a pgk-Neo(R) cassette (cEmu(N/N) mice). The cEmu(Delta/Delta) mice had reduced B cell numbers, in association with impaired D to J(H) and V(H) to DJ(H) rearrangement, whereas cEmu(N/N) mice had a complete block in IgH V(D)J(H) recombination, confirming that additional cis elements cooperate with iEmu to enforce D to J(H) recombination. In addition, developing cEmu(Delta/Delta) and cEmu(N/N) B lineage cells had correspondingly decreased levels of germ-line transcripts from the J(H) region of the IgH locus (mu0 and Imu transcripts); although both had normal levels of germ-line V(H) transcripts, suggesting that cEmu may influence IgH locus V(D)J recombination by influencing accessibility of J(H) proximal regions of the locus. Consistent with chimera studies, peripheral cEmu(Delta/Delta) B cells had normal surface Ig and relatively normal class switch recombination. However, cEmu(Delta/Delta) B cells also had relatively normal somatic hypermutation of their IgH variable region genes, showing unexpectedly that the cEmu is not required for this process. The availability of mice with the iEmu mutation in their germ line will facilitate future studies to elucidate the roles of iEmu in V(H)(D)J(H) recombination in the context of IgH chromatin structure and germ-line transcription.
Novel 3-Pyridyl Ethers with Subnanomolar Affinity for Central Neuronal Nicotinic Acetylcholine Receptors (1996)

Recent evidence indicating the therapeutic potential of cholinergic channel modulators for the treatment of central nervous system (CNS) disorders as well as the diversity of brain neuronal nicotine acetylcholine receptors (nAChRs) have suggested an opportunity to develop subtype-selective nAChR ligands for the treatment of specific CNS disorders with reduced side effect liabilities. We report a novel series of 3-pyridyl ether compounds which possess subnanomolar affinity for brain nAChRs and differentially activate subtypes of neuronal nAChRs. The synthesis and structure-activity relationships for the leading members of the series are described, including A-85380 (4a), which possesses ca.50 pM affinity for rat brain [(3)H]-(-)-cytisine binding sites and 163% efficacy compared to nicotine to stimulate ion flux at human alpha4beta2 nAChR subtype, and A-84543 (2a), which exhibits 84-fold selectivity to stimulate ion flux at human alpha4beta2 nAchR subtype compared to human ganglionic type nAChRs. Computational studies indicate that a reasonable superposition of a low energy conformer of 4A with (S)-nicotine and (-)-epibatidine can be achieved.
Detection of Glucose, Galactose, and Lactose in Milk with a Microdialysis-Coupled Flow Injection Amperometric Sensor (2002)

A microdialysis-coupled flow injection amperometric Sensor (FIAS) was used to determine glucose, galactose, and lactose in milk. The sensor is based on enzymecatalyzed reaction in combination with the three wellestablished analytical techniques, namely; microdialysis sampling, flow injection analysis (FIA), and amperometric detection. With the multianalyte sensor it was possible to detect glucose and galactose by sequential injection of their corresponding oxidase enzymes: glucose oxidase and galactose oxidase, while lactose was determined by injection of a mixture of beta-galactosidase and glucose oxidase enzymes. The sensor showed a linear response between 0.05 and 10 mM for glucose, between 0.1 and 20 mM for galactose and between 0.2 and 20 mM for lactose, respectively. The relative standard deviation values of the sensor measurements for glucose, galactose, and lactose were 3-4% (n = 3). The sensor measurements for lactose content in milk were compared with a standard method with an infrared spectrophotometer.
Latent Ruthenium Olefin Metathesis Catalysts That Contain an N-Heterocyclic Carbene Ligand (2004)

A new N-heterocyclic carbene containing olefin metathesis catalyst, (sIMes)(Cl)2Ru(CH(CH2)2-C,N-2-C5H4N) (4a), was synthesized from (sIMes)(PCy3)(Cl)2RuCHPh (1) or (sIMes)(py)2(Cl)2RuCHPh (3). When heated at 40 °C in dichloromethane, 4a is slowly converted to its isomer 4b. The X-ray structures of 4a and 4b show that the NHC and pyridine ligands are trans in 4a and cis in 4b. 4a is more latent than 1 and 4b much more latent than 4a in ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROMP).
Structure of a DNA Glycosylase Searching for Lesions (2006)

DNA glycosylases must interrogate millions of base pairs of undamaged DNA in order to locate and then excise one damaged nucleobase. The nature of this search process remains poorly understood. Here we report the use of disulfide cross-linking (DXL) technology to obtain structures of a bacterial DNA glycosylase, MutM, interrogating undamaged DNA. These structures, solved to 2.0 angstrom resolution, reveal the nature of the search process: The protein inserts a probe residue into the helical stack and severely buckles the target base pair, which remains intrahelical. MutM therefore actively interrogates the intact DNA helix while searching for damage.
Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence (2004)

Oncogenic stimuli are thought to induce senescence in normal cells in order to protect against transformation and to induce proliferation in cells with altered p53 and/or retinoblastoma (Rb) pathways. In human fibroblasts, RAS initiates senescence through upregulation of the cyclin-dependent kinase inhibitor p16INK4A. We show here that in contrast to cultured fibroblast strains, freshly isolated normal fibroblasts are resistant to RAS-induced senescence and instead show some characteristics of transformation. RAS did not induce growth arrest or expression of senescence-associated beta-galactosidase, and Rb remained hyperphosphorylated despite elevated levels of p16. Instead, RAS promoted anchorage-independent growth of normal fibroblasts, although expression of hTert with RAS increased colony formation and allowed normal fibroblasts to bypass contact inhibition. To test the hypothesis that p16 levels determine how cells respond to RAS, we expressed RAS in freshly isolated fibroblasts that expressed very low levels of p16, in hTert-immortalized fibroblasts that had accumulated intermediate levels of p16, and in IMR90 fibroblasts with high levels of p16. RAS induced growth arrest in cells with higher p16 levels, and this effect was reversed by p16 knockdown in the hTert-immortalized fibroblasts. These findings indicate that culture-imposed stress sensitizes cells to RAS-induced arrest, whereas early passage cells do not arrest in response to RAS.
Potential blood-based markers of celiac disease (2014)

The CD markers identified in this study further emphasize the significance of components related to NF-κB regulation in relation to CD. However, the relevance of CXCL11, TNFSF13B, TNFRSF9, and other NF-κB interacting proteins recognized by pathway analysis, needs to be further investigated in relation to diagnosis and monitoring of CD.
Artemisinins and synthetic trioxolanes in the treatment of helminth infections (2007)

Artemisinin-based combination therapies are increasingly deployed against malaria, and hence there is a need to assess the potential auxiliary effects against schistosomiasis in settings where both diseases are endemic. Also, the effect of artemisinin-based combination therapies on food-borne trematodiasis should be assessed. In-vitro and in-vivo findings with the synthetic trioxolanes provide data to launch preclinical investigations.
Joint quantization and error diffusion of color images using competitive learning (2002)

A competitive learning scheme for color image quantization is elaborated, in which the dithering process for eliminating contouring effects, instead of performed a posteriori, is imbedded in the quantization process. Quantization is performed by clustering in color space. The dithering process is a simple error diffusion which diffuses the quantization error made by one pixel to its local neighborhood. For small color palettes, this is demonstrated to improve the visual quality of quantized images.
Activation of Integrin Function by Nanopatterned Adhesive Interfaces (2004)

To study the function behind the molecular arrangement of single integrins in cell adhesion, we designed a hexagonally close-packed rigid template of cell-adhesive gold nanodots coated with cyclic RGDfK peptide by using block-copolymer micelle nanolithography. The diameter of the adhesive dots is < 8 nm, which allows the binding of one integrin per dot. These dots are positioned with high precision at 28, 58, 73, and 85 nm spacing at interfaces. A separation of > or = 73 nm between the adhesive dots results in limited cell attachment and spreading, and dramatically reduces the formation of focal adhesion and actin stress fibers. We attribute these cellular responses to restricted integrin clustering rather than insufficient number of ligand molecules in the cell-matrix interface since "micro-nanopatterned" substrates consisting of alternating fields with dense and no nanodots do support cell adhesion. We propose that the range between 58-73 nm is a universal length scale for integrin clustering and activation, since these properties are shared by a variety of cultured cells.
Pathology, diagnosis, and classification of pressure ulcers: comparing clinical and imaging techniques (2005)

Pressure ulcer classification systems are based on the clinical manifestations of the skin and tissue layer affected rather than underlying pathology. The objective of this study was to compare the validity of the clinical grading of erythema (blanching and nonblanching) with a measurement of skin perfusion. Therefore, an exploratory study comparing erythema with laser Doppler imaging of the sacrum and buttock skin areas was undertaken. Acute and major elective general, vascular, and orthopedic surgical in-patients, aged 55 years or over with an expected length of hospital stay of 5 or more days were recruited. Fifty laser Doppler images from 37 patients were obtained and included in a discriminant analysis. Discriminant analysis suggested that blanching and nonblanching erythema were physiologically distinct from "normal" skin; clinically, these could be assessed with reasonable accuracy. Imaging also determined that high blood flow of differing intensity characterized blanching and nonblanching erythema. There was no evidence of the "no flow" phenomenon.
Graphene Transistors with Multifunctional Polymer Brushes for Biosensing Applications (2014)

Exhibiting a combination of exceptional structural and electronic properties, graphene has a great potential for the development of highly sensitive sensors. To date, many challenging chemical, biochemical, and biologic sensing tasks have been realized based on graphene. However, many of these sensors are rather unspecific. To overcome this problem, for instance, the sensor surface can be modified with analyte-specific transducers such as enzymes. One problem associated with the covalent attachment of such biomolecular systems is the introduction of crystal defects that have a deleterious impact on the electronic properties of the sensor. In this work, we present a versatile platform for biosensing applications based on polymer-modified CVD-grown graphene transistors. The functionalization method of graphene presented here allows one to integrate several functional groups within surface-bound polymer brushes without the introduction of additional defects. To demonstrate the potential of this polymer brush functionalization scaffold, we modified solution-gated graphene field-effect transistors with the enzyme acetylcholinesterase and a transducing group, allowing the detection of the neurotransmitter acetylcholine. Taking advantage of the transducing capability of graphene transistors and the versatility of polymer chemistry and enzyme biochemistry, this study presents a novel route for the fabrication of highly sensitive, multipurpose transistor sensors that can find application for a multitude of biologically relevant analytes.
A New and Reliable Method of Securing Skin Grafts to the Difficult Recipient Bed (1998)

Schneider, Andrew M. M.D.; Morykwas, Michael J. Ph.D.; Argenta, Louis C. M.D. Author Information
Adhesion of pancreatic beta cells to biopolymer films (2009)

Dramatic reversal of Type 1 diabetes in patients receiving pancreatic islet transplants continues to prompt vigorous research concerning the basic mechanisms underlying patient turnaround. At the most fundamental level, transplanted islets must maintain viability and function in vitro and in vivo and should be protected from host immune rejection. Our previous reports showed enhancement of islet viability and insulin secretion per tissue mass for small islets (<125 mum) as compared with large islets (>125 mum), thus, demonstrating the effect of enhancing the mass transport of islets (i.e. increasing tissue surface area to volume ratio). Here, we report the facile dispersion of rat islets into individual cells that are layered onto the surface of a biopolymer film towards the ultimate goal of improving mass transport in islet tissue. The tightly packed structure of intact islets was disrupted by incubating in calcium-free media resulting in fragmented islets, which were further dispersed into individual or small groups of cells by using a low concentration of papain. The dispersed cells were screened for adhesion to a range of biopolymers and the nature of cell adhesion was characterized for selected groups by quantifying adherent cells, measuring the surface area coverage of the cells, and immunolabeling cells for adhesion proteins interacting with selected biopolymers. Finally, beta cells in suspension were centrifuged to form controlled numbers of cell layers on films for future work determining the mass transport limitations in the adhered tissue constructs. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 676-685, 2009.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.
Phosphororganische Verbindungen, XXXV. PO‐aktivierte Verbindungen als Olefinierungsreagentien (1962)

Abstract Mit metallierten Mono‐ und Bis‐phosphon‐ und ‐phosphinsäureestern sowie Phosphinoxyden werden Mono‐ bzw. Bis‐Olefinierungen von Carbonylverbindungen durchgeführt. Phosphonsäureester mit gesättigtem Alkylrest werden durch das Metallierungsmittel gespalten und sind im Gegensatz zu den Alkylphosphinoxyden als Olefinierungsreagentien ungeeignet. Der Einfluß verschiedener Faktoren wie Metallierungsmittel, Molverhältnis, Temperatur und Lösungsmittel auf den Reaktionsverlauf wird untersucht.
Total Synthesis of (±)-Ginkgolide B (1999)

The total synthesis of the potent PAF antagonist ginkgolide B has been accomplished. The complex\narchitecture of ginkgolide B which includes six rings, eleven stereogenic centers, ten oxygenated carbons, and\nfour contiguous fully substituted carbons is a daunting challenge for chemical synthesis. The synthesis of\nginkgolide B was accomplished through a stereoselective intramolecular photocycloaddition of enone &lt;b&gt;5&lt;/b&gt; to\nconstruct the congested core of the molecule. The photocycloaddition substrate was prepared through technology\nfor the construction of carboalkoxycyclopentenones previously reported from these laboratories. Regioselective\ncyclobutane fragmentation and further functionalization of the photoadduct &lt;b&gt;4&lt;/b&gt; provided the key pentacyclic\nintermediate. Acid-catalyzed rearrangement and epoxide opening were key transformations in the production\nof ginkgolide B from the pentacyclic intermediate.