gebhart/patrepeval huggingface dataset:
Regulation of NMDA receptors by cyclin-dependent kinase-5 (2001)

Members of the N-methyl-d-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders in the central nervous system. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.
Self-Sealed Vertical Polymeric Nanoporous-Junctions for High-Throughput Nanofluidic Applications (2008)

We developed a reliable but simple integration method of polymeric nanostructure in a poly(dimethylsiloxane) (PDMS)-based microfluidic channel, for nanofluidic applications. The Nafion polymer junction was creased by infiltrating polymer solution between the gaps created by mechanical cutting, without any photolithography or etching processes. The PDMS can seal itself with the heterogeneous polymeric nanoporous material between the PDMS/PDMS gap due to its flexibility without any (covalent) bonding between PDMS and the polymer materials. Thus, one can easily integrate the nanoporous-junction into a PDMS microchip in a leak-free manner with excellent repeatability. We demonstrated nanofluidic preconcentration of proteins (beta-phycoerythrin) using the device. Because the polymeric junction spans across the entire microchannel height, the preconcentration was achieved with high-pressure field or even in large channels, with the dimensions of 1000 microm width x 100 microm depth.
NCAM‐fibronectin‐type‐III‐domain substrata with and without a six‐amino‐acid‐long proline‐rich insert increase the dendritic and axonal arborization of spinal motoneurons (1997)

The neural cell adhesion molecule (NCAM) is a modulator of neurite outgrowth in vitro and in vivo. To see if single or tandem extracellular NCAM domains can influence neurite outgrowth, motoneurons from embryonic rat spinal cord were cultured on several NCAM fusion protein substrata. Motoneurons growing on either of two fusion proteins comprising the combined two fibronectin type III homology domains of NCAM with or without a six-amino-acid-long, proline-rich insert (F3I,II+ and F3I,II, respectively) usually developed three or more neurites per cell. Motoneurons grown on NCAM-immunoglobulin domain I (IgI), by contrast, developed many unipolar and bipolar cells, a situation also seen when motoneurons were cultured on control substrata. The neuritic trees of motoneurons grown on F3I,II and F3I,II+ appeared broader and rounder than motoneurons cultured on either control or IgI substrata, and the spreading indices of motoneurons grown on F3I,II and F3I,II+ were significantly lower than when the other substrata were used. Neither of the NCAM-F3 fusion proteins stimulated the outgrowth of single neurites. By contrast, IgI substratum was able to stimulate neurite outgrowth over control substrata. Both NCAM-F3 substrata induced branches in axons and dendrites, whereas IgI substratum did not affect neurite branching significantly. These data indicated that neurite outgrowth and neurite branching on the chosen substrata were not closely linked to each other. Furthermore, the branching characteristics of motoneuron neurites potentially depend on their differentiation states and, possibly, on the conformation of the two NCAM-F3 domains. J. Neurosci. Res. 48:112–121, 1997. © 1997 Wiley-Liss, Inc.
Exploratory phase II efficacy study of MORAb-003, a monoclonal antibody against folate receptor alpha, in platinum-sensitive ovarian cancer in first relapse (2008)

5500 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. MORAb-003 is a humanized monoclonal antibody to FRA. Binding of MORAb-003 to FRA blocks phosphorylation by Lyn kinase; mediates FRA-expressing tumor cell killing; and suppresses tumor growth in xenograft models. A phase 1 study of single agent (SA) MORAb-003 showed no significant AEs and suggested efficacy in platinum-resistant EOC. This study was designed to determine the efficacy of MORAb-003 as a SA, or with platinum and taxane (P/T) in recurrent, platinum-sensitive EOC. Methods: Subjects with platinum sensitive EOC in first relapse are eligible. For CA-125 elevation without symptoms (± measurable disease) the subject receives SA MORAb- 003 until progression. For symptomatic relapse or progression with SA the subject receives P/T and MORAb-003. Subjects with CR or PR receive SA MORAb-003 maintenance therapy. Results: 52 subjects have enrolled. Few drug-related adverse events have been reported with MORAb-003 alone or MORAb-003 with P/T. In subjects receiving MORAb-003 with P/T, CA-125 has normalized in 58% after 2 cycles, 88% completing 4 cycles and 100% of subjects completing 6 cycles. RECIST scores improved in parallel. Historically only 35–55% of patients treated with chemotherapy alone achieve a second remission. To date, 3/8 evaluable subjects have achieved a second remission longer than the first; 26 additional subjects are being observed for this endpoint on therapy. Subjects on SA MORAb-003 have shown transient responses of CA-125, but not complete normalization. Conclusions: MORAb-003 with P/T significantly increases ORR compared to historic data for P/T alone, and increases the duration of second compared to first remission Based on these data, additional studies of MORAb- 003 with chemotherapy in platinum-sensitive and platinum-resistant EOC are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Morphotek Morphotek Morphotek
Swarm Intelligence: A New C2 Paradigm with an Application to Control Swarms of UAVs (2003)

We have developed an agent-based model to simulate command and control of a swarm of Unmanned Air Vehicles (UAVs). Our approach makes use of decentralized strategies to control a UAV swarm carrying out a search mission. In this paper we introduce our approach, we present the details of the proposed model, and we provide results of simulations testing our control strategies under a variety of configurations. We also outline some initial results obtained by extending our simulation tool to include the ability to carry out missions in which UAVs can track moving targets, strike targets, and perform Battle Damage Assessment.
OFDM or single-carrier block transmissions? (2004)

We compare two block transmission systems over frequency-selective fading channels: orthogonal frequency-division multiplexing (OFDM) versus single-carrier modulated blocks with zero padding (ZP). We first compare their peak-to-average power ratio (PAR) and the corresponding power amplifier backoff for phase-shift keying or quadrature amplitude modulation. Then, we study the effects of carrier frequency offset on their performance and throughput. We further compare the performance and complexity of uncoded and coded transmissions over random dispersive channels, including Rayleigh fading channels, as well as practical HIPERLAN/2 indoor and outdoor channels. We establish that unlike OFDM, uncoded block transmissions with ZP enjoy maximum diversity and coding gains within the class of linearly precoded block transmissions. Analysis and computer simulations confirm the considerable edge of ZP-only in terms of PAR, robustness to carrier frequency offset, and uncoded performance, at the price of slightly increased complexity. In the coded case, ZP is preferable when the code rate is high (e.g., 3/4), while coded OFDM is to be preferred in terms of both performance and complexity when the code rate is low (e.g., 1/2) and the error-correcting capability is enhanced. As ZP block transmissions can approximate serial single-carrier systems as well, the scope of the present comparison is broader.
A phase I clinical study to evaluate safety of orally administered, genetically engineeredSalmonella entericaserovarTyphimuriumfor canine osteosarcoma (2016)

We conducted a prospective phase I study to evaluate safety of an orally administered <i>Salmonella</i> encoding IL-2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of doxorubicin and six doses of SalpIL2. There were six reportable events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving SalpIL2 had significantly longer disease-free interval (DFI) than a comparison group of dogs treated with doxorubicin alone. Dogs treated using lower doses of SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The data indicate that SalpIL2 is safe and well tolerated, which supports additional testing to establish the potential for SalpIL2 as a novel form of adjuvant therapy for dogs with osteosarcoma.
Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody (2010)

AMG 386 is an investigational first-in-class peptide-Fc fusion protein (peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 (Ang1) and Ang2 with their receptor, Tie2. Although the therapeutic value of blocking Ang2 has been shown in several models of tumorigenesis and angiogenesis, the potential benefit of Ang1 antagonism is less clear. To investigate the consequences of Ang1 neutralization, we have developed potent and selective peptibodies that inhibit the interaction between Ang1 and its receptor, Tie2. Although selective Ang1 antagonism has no independent effect in models of angiogenesis-associated diseases (cancer and diabetic retinopathy), it induces ovarian atrophy in normal juvenile rats and inhibits ovarian follicular angiogenesis in a hormone-induced ovulation model. Surprisingly, the activity of Ang1 inhibitors seems to be unmasked in some disease models when combined with Ang2 inhibitors, even in the context of concurrent vascular endothelial growth factor inhibition. Dual inhibition of Ang1 and Ang2 using AMG 386 or a combination of Ang1- and Ang2-selective peptibodies cooperatively suppresses tumor xenograft growth and ovarian follicular angiogenesis; however, Ang1 inhibition fails to augment the suppressive effect of Ang2 inhibition on tumor endothelial cell proliferation, corneal angiogenesis, and oxygen-induced retinal angiogenesis. In no case was Ang1 inhibition shown to (a) confer superior activity to Ang2 inhibition or dual Ang1/2 inhibition or (b) antagonize the efficacy of Ang2 inhibition. These results imply that Ang1 plays a context-dependent role in promoting postnatal angiogenesis and that dual Ang1/2 inhibition is superior to selective Ang2 inhibition for suppression of angiogenesis in some postnatal settings.
Software transactional memory for dynamic-sized data structures (2003)

We propose a new form of software transactional memory (STM) designed to support dynamic-sized data structures, and we describe a novel non-blocking implementation. The non-blocking property we consider is obstruction-freedom. Obstruction-freedom is weaker than lock-freedom; as a result, it admits substantially simpler and more efficient implementations. A novel feature of our obstruction-free STM implementation is its use of modular contention managers to ensure progress in practice. We illustrate the utility of our dynamic STM with a straightforward implementation of an obstruction-free red-black tree, thereby demonstrating a sophisticated non-blocking dynamic data structure that would be difficult to implement by other means. We also present the results of simple preliminary performance experiments that demonstrate that an "early release" feature of our STM is useful for reducing contention, and that our STM lends itself to the effective use of modular contention managers.
Regulation and Function of Escherichia coli Sugar Efflux Transporter A (SetA) during Glucose-Phosphate Stress (2010)

Accumulation of certain nonmetabolizable sugar-phosphates (including α-methyl glucoside-6-phosphate) in Escherichia coli is growth inhibitory and elicits the glucose-phosphate stress response. The transcription factor SgrR activates transcription of the small RNA SgrS under stress conditions. SgrS represses translation of mRNAs encoding sugar transporters. The sgrR and sgrS genes are located directly upstream of setA, and this gene organization is conserved in numerous enteric species, prompting the hypothesis that SetA contributes to the glucose-phosphate stress response. SetA is a proton motive force-driven efflux pump capable of transporting various sugars and sugar analogs in vitro. This study demonstrates that setA expression is induced in response to glucose-phosphate stress, and this requires SgrR. Under stress conditions, setA is cotranscribed with sgrS from the sgrS promoter. A setA mutant exhibits a growth defect under stress conditions that can be complemented by setA in trans, suggesting that SetA contributes to the optimal cellular recovery from stress. Despite previous in vitro evidence that SetA can promote efflux of the stress-causing glucose analog α-methyl glucoside, in vivo data in this study indicate that SetA is not the major efflux pump responsible for removal of α-methyl glucoside under stress conditions.
Simple and Efficient Solution-Phase Synthesis of Oligonucleotides Using Extractive Work-Up (2006)

A solution-phase synthesis protocol amenable to scale-up was developed for the preparation of oligonucleotides employing phosphoramidite chemistry and DMTr/iBu/Bz-protected monomers. Isolation of intermediates was accomplished by means of extractions as the only purification tool. The potential of the method is demonstrated with the synthesis of a hexameric DNA fragment in high yield and purity.
Role of carbohydrate in the function of human granulocyte-macrophage colony-stimulating factor (1987)

cDNA clones for the human hematopoietic regulator granulocyte-macrophage colony-stimulating factor (hGM-CSF) were isolated from a lamba gt11 cDNA library prepared from RNA of COS cells transiently expressing the gene for hGM-CSF. As the RNA was a rich source of hGM-CSF mRNA, approximately 0.1% of the clones of this library contained hGM-CSF sequences. All of the clones analyzed were full length and were correctly processed. When subcloned into an expression vector and transfected into COS cells, the cDNA clones direct the synthesis of higher levels of the growth factor than the gene from which they were derived. The cDNA for native hGM-CSF was used to generate structural mutants which lack N-linked carbohydrate, O-linked carbohydrate, or both. Although the mutant proteins had differing specific activities, the nonglycosylated forms reproduce many, if not all, of the physiologic functions of authentic hGM-CSF. The role of carbohydrate in the secretion and function of hGM-CSF is discussed.
Involvement of ER stress in retinal cell death. (2007)

These data indicate that ER-stress may play a pivotal role in RGC death, whether induced by NMDA or IOP elevation.
ChemInform Abstract: Taxanes: An Unusual Class of Natural Products (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Ally: OS-Transparent Packet Inspection Using Sequestered Cores (2011)

This paper presents Ally, a server platform architecture that supports compute-intensive management services on multi-core processors. Ally introduces simple hardware mechanisms to sequester cores to run a separate software environment dedicated to management tasks, including packet processing software appliances (e.g. for Deep Packet Inspection, DPI) with efficient mechanisms to safely and transparently intercept network packets. Ally enables distributed deployment of compute-intensive management services throughout a data center. Importantly, it uniquely allows these services to be deployed independent of the arbitrary OSs and/or hyper visor that users may choose to run on the remaining cores, with hardware isolation preventing the host environment from tampering with the management environment. Experiments using full system emulation and a Linux-based prototype validate Ally functionality and demonstrate low overhead packet interception, e.g., using Ally to host the well-known Snort packet inspection software incurs less over-head than deploying Snort as a Xen virtual machine appliance, resulting in up to 2× improvement in throughput for some workloads.
Assessing the Emergence of Resistance: The Absence of Biological Cost In Vivo May Compromise Fosfomycin Treatments for P. aeruginosa Infections (2010)

We have reached the conclusion that the use of fosfomycin for P. aeruginosa infections, even in combined therapy, might not be as promising as expected. This study should encourage the scientific community to assess the in vivo cost of resistance for specific antibiotic-bacterial species combinations, and therefore avoid reaching universal conclusions from single model organisms.
Supramolecular Drug‐Delivery Systems Based on Polymeric Core–Shell Architectures (2003)

Hitting the target: Although the cellular uptake of supramolecular nanocarriers by endocytosis is not cell-specific, a high passive selectivity has been observed in porous tissues, such as tumor tissue. The encapsulated, often toxic, drug is efficiently shielded and can develop its activity by selective release from the nanocarrier upon a shift of the pH value in the tumor tissue or inside the cell (see scheme).
Norms and Standards for Pyrolysis Liquids. End-User Requirements and Specifications (2005)

The commercialization of biomass-derived pyrolysis liquids for use in heat and power applications is dependent on the ability to successfully provide a fuel of acceptable quality to an end user at a competitive price. One of the intentions of the European Union (EU) Altener 4.1030/C/00-015/2000 project was to derive standards for biomass-derived pyrolysis liquids, based on a consensus between providers of the equipment (boilers, engines, and turbines) and the producers of the liquids. Five basic properties (homogeneity, water content, solids content, stability, flash point) for the liquids are used as the primary criteria for pyrolysis liquid evaluation. Specific values are proposed to ensure that pyrolysis liquids meet a minimum grade that is acceptable for use as a fuel oil in boilers and engines. Data on emissions from boilers, engines and turbines are presented. Preliminary long-duration test data from boiler use are available to allow more-detailed specifications on secondary properties to be made. The purpose of this work is to ensure that a realistic set of specifications is determined, to allow the introduction of pyrolysis liquids into existing fuel infrastructures and markets.
A new loading algorithm for discrete multitone transmission (2002)

A new loading algorithm for discrete multitone transmission is proposed. Thereby rate is not distributed according to channel capacity, but rate and transmit power are assigned to maximize the signal-to-noise ratio in each carrier. Because closed form expressions can be derived the algorithm is of very low complexity, even lower than the loading algorithm recently proposed by Chow et al. (see IEEE Transactions on Communications, no.2/3/4, p.773-5, 1995). Nevertheless achievable performance is higher or at least the same. Results for a typical high rate transmission over twisted pair lines are presented.
High-performance liquid chromatographic separation of high-molecular-weight polycyclic aromatic compounds in carbon black (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHigh-performance liquid chromatographic separation of high-molecular-weight polycyclic aromatic compounds in carbon blackPaul A. Peaden, Milton L. Lee, Yukio. Hirata, and Milos. NovotnyCite this: Anal. Chem. 1980, 52, 14, 2268–2271Publication Date (Print):December 1, 1980Publication History Published online1 May 2002Published inissue 1 December 1980https://pubs.acs.org/doi/10.1021/ac50064a008https://doi.org/10.1021/ac50064a008research-articleACS PublicationsRequest reuse permissionsArticle Views248Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Conserved Sequence and Structural Elements in the HIV-1 Principal Neutralizing Determinant (1990)

The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part of a disulfide bridged loop in the third variable region of the external envelope protein, gp120. Analysis of the amino acid sequences of this domain from 245 different HIV-1 isolates revealed that the PND is less variable than thought originally. Conservation to better than 80 percent of the amino acids in 9 out of 14 positions in the central portion of the PND and the occurrence of particular oligopeptide sequences in a majority of the isolates suggest that there are constraints on PND variability. One constraining influence may be the structural motif (beta strand--type II beta turn--beta strand--alpha helix) predicted for the consensus PND sequence by a neural network approach. Isolates with a PND similar to the commonly investigated human T cell lymphoma virus IIIB (HTLV-IIIB) and LAV-1 (BRU) strains were rare, and only 14 percent of sera from 86 randomly selected HIV-1 seropositive donors contained antibodies that recognized the PND of these virus isolates. In contrast, over 65 percent of these sera reacted with peptides containing more common PND sequences. These results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.