gebhart/patrepeval huggingface dataset:
From DNA sequence to improved functionality: using protein sequence comparisons to rapidly design a thermostable consensus phytase (2000)

Naturally-occurring phytases having the required level of thermostability for application in animal feeding have not been found in nature thus far. We decided to de novo construct consensus phytases using primary protein sequence comparisons. A consensus enzyme based on 13 fungal phytase sequences had normal catalytic properties, but showed an unexpected 15-22 degrees C increase in unfolding temperature compared with each of its parents. As a first step towards understanding the molecular basis of increased heat resistance, the crystal structure of consensus phytase was determined and compared with that of Aspergillus niger phytase. Aspergillus niger phytase unfolds at much lower temperatures. In most cases, consensus residues were indeed expected, based on comparisons of both three-dimensional structures, to contribute more to phytase stabilization than non-consensus amino acids. For some consensus amino acids, predicted by structural comparisons to destabilize the protein, mutational analysis was performed. Interestingly, these consensus residues in fact increased the unfolding temperature of the consensus phytase. In summary, for fungal phytases apparently an unexpected direct link between protein sequence conservation and protein stability exists.
Characterization of spatially varying surface waves in a land seismic survey (2008)

We present several methods for analyzing surface waves in a highly sampled 3‐C, 3D survey, and report the most important characteristics derived from those analyses. In particular, we demonstrate the spatial variability of surface‐wave velocities and polarization properties. We also show that surface‐wave velocities are correlated with other seismic and nonseismic properties of the near surface, such as shear‐wave statics and surface texture derived from satellite imagery.
Maintenance of transplantation potential in ex vivo expanded CD34(+)- selected human peripheral blood progenitor cells (1994)

CD34(+)-selected hematopoietic progenitor cells are being increasingly used for autotransplantation, and recent evidence indicates that these cells can be expanded ex vivo. Of 15 patients with solid tumors undergoing a phase I/II clinical trial using CD34(+)-selected peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy, we analyzed the frequency of long-term culture-initiating cells (LTCIC) as a measure of transplantation potential before and after ex vivo expansion of CD34+ cells. PBPCs were mobilized by combination chemotherapy and granulocyte colony-stimulating factor (G-CSF). The original unseparated leukapheresis preparations, the CD34(+)-enriched transplants, as well as nonabsorbed fractions eluting from the CD34 immunoaffinity columns (Ceprate; CellPro, Bothell, WA) were monitored for their capacity to repopulate irradiated allogeneic stroma in human long-term bone marrow cultures. We found preservation of more than three quarters of fully functional LTCIC in the CD34(+)-selected fractions. Quantitation of LTCIC by limiting dilution analysis showed a 53-fold enrichment of LTCIC from 1/9,075 in the unseparated cells to an incidence of 1/169 in the CD34+ fractions. Thus, in a single apheresis, it was possible to harvest a median of 1.65 x 10(4) LTCIC per kg body weight (range, 0.71 to 3.72). In addition, in six patients, large-scale ex vivo expansions were performed using a five-factor cytokine combination consisting of stem cell factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin (EPO), previously shown to expand committed progenitor cells. LTCIC were preserved, but not expanded during the culture period. Optimization of ex vivo expansion growth factor requirements using limiting dilution assays for LTCIC estimation indicated that the five-factor combination using SCF, IL-1, IL-3, IL-6, and EPO together with autologous plasma was the most reliable combination securing both high progenitor yield and, at the same time, optimal preservation of LTCIC. Our data suggest that ex vivo-expanded CD34+ PBPCs might be able to allow long-term reconstitution of hematopoiesis.
A conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope. (1987)

A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV+ patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did not react in RIA and neutralized HIV in vitro. Thus, approximately 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays.
Dilute solution characterization of cyclic polystyrene molecules and their zero-shear viscosity in the melt (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDilute solution characterization of cyclic polystyrene molecules and their zero-shear viscosity in the meltG. B. McKenna, G. Hadziioannou, P. Lutz, G. Hild, C. Strazielle, C. Straupe, P. Rempp, and A. J. KovacsCite this: Macromolecules 1987, 20, 3, 498–512Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March 1987https://doi.org/10.1021/ma00169a007RIGHTS & PERMISSIONSArticle Views1096Altmetric-Citations185LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
Identification of Plasma Proteases Inhibited by Manduca sexta Serpin-4 and Serpin-5 and Their Association with Components of the Prophenol Oxidase Activation Pathway (2005)

One innate immune response pathway of insects is a serine protease cascade that activates prophenol oxidase (pro-PO) in plasma. However, details of this pathway are not well understood, including the number and order of proteases involved. Protease inhibitors from the serpin superfamily appear to regulate the proteases in the pathway. Manduca sexta serpin-4 and serpin-5 suppress pro-PO activation in plasma, apparently by inhibiting proteases upstream of the direct activator of pro-PO. To identify plasma proteases inhibited by these serpins, we used immunoaffinity chromatography with serpin antibodies to isolate serpin-protease complexes that formed after activation of the cascade by exposure of plasma to bacteria or lipopolysaccharide. Covalent complexes of serpin-4 with hemolymph proteases HP-1 and HP-6 appeared in plasma activated by Gram-positive or Gram-negative bacteria, whereas serpin-4 complexes with HP-21 and two unidentified proteases were unique to plasma treated with Gram-positive bacteria. HP-1 and HP-6 were also identified as target proteases of serpin-5, forming covalent complexes after bacterial activation of the cascade. These results suggest that HP-1 and HP-6 may be components of the pro-PO activation pathway, which are activated in response to infection and regulated by serpin-4 and serpin-5. HP-21 and two unidentified proteases may participate in a Gram-positive bacteria-specific branch of the pathway. Several plasma proteins that co-purified with serpin-protease complexes, most notably immulectins and serine protease homologs, are known to be components of the pro-PO activation pathway. Our results suggest that after activation by exposure to bacteria, components of the pro-PO pathway associate to form a large noncovalent complex, which localizes the melanization reaction to the surface of invading microorganisms.
Chondroitin Sulfate E Fragments Enhance CD44 Cleavage and CD44-Dependent Motility in Tumor Cells (2008)

During tumor cell invasion, certain extracellular matrix (ECM) components such as hyaluronan (HA) are degraded into small oligosaccharides, which are detected in patients. We previously reported that such HA oligosaccharides induce the proteolytic cleavage of an ECM-binding molecule CD44 from tumor cells and promote tumor cell migration in a CD44-dependent manner. Here, we report that chondroitin sulfate E (CSE), another component of the tumor ECM, strongly enhances CD44 cleavage and tumor cell motility when degraded into oligosaccharides. CSE and its degradation products were detected in pancreatic ductal adenocarcinoma. In CD44-expressing pancreatic tumor cells, degraded forms of CSE but not intact CSE enhanced CD44 cleavage; enzymatic digestion of such low-molecular weight CSE (LMW-CSE) abrogated this enhancement. Among the LMW-CSE preparations examined, 3-kDa CSE most potently induced CD44 cleavage. Nuclear magnetic resonance analysis showed that the 3-kDa-CSE bound to CD44, and that blocking such binding abrogated the CD44 cleavage induction. LMW-CSE also induced prominent filopodia formation and cytoskeletal changes in tumor cells; these effects were also abrogated by blocking the LMW-CSE binding to CD44. Chemically synthesized CSE hexasaccharides also enhanced the CD44 cleavage and tumor cell motility in a CD44-dependent manner. We conclude that the degraded forms of CSE modulate cell adhesion and migration by interacting with tumor-cell CD44, suggesting that the degradation products of tumor-associated ECMs that interact with CD44 play a significant role in CD44-mediated tumor progression.
Abstract 2448: h224G11, a humanized whole antibody targeting the c-Met receptor, induces c-Met down-regulation and triggers ADCC functions (2010)

Abstract c-Met is the prototypic member of a sub-family of receptor tyrosine kinases (RTK) which also includes RON and SEA. The c-Met RTK family is structurally different from other RTK families and is the only known high-affinity receptor for hepatocyte growth factor (HGF), also called scatter factor (SF). While the controlled regulation of c-Met and HGF are essential for in mammalian development, tissue maintenance and repair, their deregulation is implicated in the progression of cancers. Aberrant signalling of c-Met can arise by ligand-dependent and independent mechanisms such as over-expression of c-Met, paracrine or autocrine activations, or through gain of function mutations. However, an oligomerization of the c-Met receptor, either in the presence or absence of the ligand, is required to regulate the binding affinity and binding kinetics of the kinase toward ATP and tyrosine-containing peptide substrates. An inappropriate c-Met activation plays a crucial role in tumorigenesis and metastasis. We have generated, a humanized anti-c-Met IgG1 monoclonal antibody (h224G11) that displays fully antagonist activities when used as a whole antibody. The h224G11 Mab exhibits a high affinity for the receptor, blocks HGF binding, inhibits c-Met phosphorylation and c-Met dimerization. These effects are presumably responsible for the inhibition of the major functions of c-Met including cell proliferation, migration, invasion but also cell scattering and angiogenesis, observed in vitro with different cell lines. In addition to these in vitro properties, h224G11 dramatically inhibits in vivo growth of autocrine (U87-MG), partially autophosphorylated (NCI-H441) and c-Met amplified cell lines (MKN45, EBC1 and Hs746T). Recent in vitro experiments demonstrate that h224G11 down-regulates c-Met on many cells including A549 and NCI-H441. Using an ELISA immunoassay, it has been shown that this down-regulation does not result from a shedding process but that h224G11 induces c-Met internalization and degradation. Similar results were obtained in ex-vivo experiments using Hs764T tumors from xenografted mice. In addition to its direct effect on c-Met modulation, the humanized antibody also triggers effector functions. A549, NCI-H441 and Hs746T were used as target cells in an ADCC chromium-released assay with human purified NK cells. In these assays, the h224G11 demonstrates a significant ADCC activity. Taken together the in vitro and in vivo data suggest that the h224G11 antibody targeting c-Met is a promising candidate for the treatment of ligand-dependent and ligand-independent tumors as a single or combined therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2448.
Advances in Boar Semen Cryopreservation (2010)

The present paper highlights aspects of the cryopreservation of boar semen, a species with particular large, fractionated ejaculates, and a cumbersome cryotechnology that had prevented its commercial application. With the dramatic increase of use of liquid pig semen for artificial breeding over the past decade, developments on cryopreservation alongside the routine use of stud boar semen for AI had been promoted. Recent advances in our laboratory, accommodating the best use of portions of the sperm-rich fraction of the ejaculate for cryopreservation of the sperm-peak portion (P1) and parallel use of the rest of the collected ejaculated spermatozoa, appears as a suitable commercial alternative.
Efficient Ridesharing Order Dispatching with Mean Field Multi-Agent Reinforcement Learning (2019)

A fundamental question in any peer-to-peer ridesharing system is how to, both effectively and efficiently, dispatch user's ride requests to the right driver in real time. Traditional rule-based solutions usually work on a simplified problem setting, which requires a sophisticated hand-crafted weight design for either centralized authority control or decentralized multi-agent scheduling systems. Although recent approaches have used reinforcement learning to provide centralized combinatorial optimization algorithms with informative weight values, their single-agent setting can hardly model the complex interactions between drivers and orders. In this paper, we address the order dispatching problem using multi-agent reinforcement learning (MARL), which follows the distributed nature of the peer-to-peer ridesharing problem and possesses the ability to capture the stochastic demand-supply dynamics in large-scale ridesharing scenarios. Being more reliable than centralized approaches, our proposed MARL solutions could also support fully distributed execution through recent advances in the Internet of Vehicles (IoV) and the Vehicle-to-Network (V2N). Furthermore, we adopt the mean field approximation to simplify the local interactions by taking an average action among neighborhoods. The mean field approximation is capable of globally capturing dynamic demand-supply variations by propagating many local interactions between agents and the environment. Our extensive experiments have shown the significant improvements of MARL order dispatching algorithms over several strong baselines on the accumulated driver income (ADI), and order response rate measures. Besides, the simulated experiments with real data have also justified that our solution can alleviate the supply-demand gap during the rush hours, thus possessing the capability of reducing traffic congestion.
An Improved Plasmid DNA Expression Vector for Direct Injection into Skeletal Muscle (1996)

In previous work, the direct injection of 50 micrograms of a plasmid DNA vector encoding firefly luciferase (VR1205) into murine quadriceps muscle produced an average of 6.5 ng of luciferase per muscle at 7 days postinjection. In this report, various elements of the VR1205 vector were modified to increase gene expression levels or to eliminate undesired viral sequences. Expression of the modified vectors was then compared to VR1205 using the intramuscular injection assay. In general, modifications to promoter, enhancer, and intronic sequences either decreased luciferase expression levels or had no effect. However, modifications to the polyadenylation and transcriptional termination sequences, plasmid backbone elements, and the luciferase gene itself each increased luciferase expression levels. The best-expressing vector, designated VR1255, contained a combination of these incrementally beneficial changes. A single intramuscular injection of 50 micrograms of VR1255 produced 300 ng of luciferase at 7 days postinjection, an expression level 46-fold higher than the VR1205 vector (or 22-fold higher, excluding modifications to the luciferase gene) and 154-fold higher than a commercially available luciferase expression vector. Thus, VR1255 represents an improved plasmid DNA vector that may be useful for gene therapy applications.
Comparative study of dilute nitride and bismide sub-junctions for tandem solar cells (2016)

Theoretical models show that tandem solar cells can reach efficiency of more than 50 %. To achieve efficiencies closer to the projected outputs in a quad tandem solar cell, a 1.0 eV sub-junction with good optical and electrical properties is sought. The observed bandgap reduction when small amounts of Nitrogen or Bismuth is incorporated into GaAs makes these alloys (dilute nitrides and bismides) possible candidates for the tandem solar cells.&#13;\nIn this work, the performance of dilute nitride and bismide solar cells of different designs which include p-i-n bulk and p-i-n multiple quantum wells (MQWs), and n-i-p-i structures are studied comparatively. Performance in this context refers to: the magnitude and quality of the dark current generated by the devices, the spectral response of the solar cells especially in the dilute nitride and bismide absorption regions, and efficiency responsivity to temperature and to elevated radiation. To achieve the latter objectives, dark and under the AM1.5G and spectral response measurements were performed on the solar cells. The results reveal that, in the dilute bulk or MQWs p-i-n and n-i-p-i solar the total dark current is nearly the dark current generated by dilute nitride or bismide material alone. The applicability of Sah-Noyce-Shockley model to bulk p-i-n dilute nitride solar cells dark current is demonstrated. The dilute nitride solar cells exhibit temperature coefficients of efficiency that are lower than that of the conventional GaAs p-n junction solar cell. MQWs solar cells show lowest sensitivity to temperature changes.&#13;\nThe dilute nitride and bismide materials show similar diode characteristics with dark currents that are dominated by non-radiative recombination mechanisms.
Using RNA Aptamers and the Proximity Ligation Assay for the Detection of Cell Surface Antigens (2008)

The detection and typing of tumor cells based on differentially or similarly expressed antigens (biomarkers) have proven to be increasingly important for the diagnosis and treatment of various cancers. Sensitive techniques for the detection of cell surface antigens are therefore crucial for the early and accurate detection of cancer. Although techniques such as ELISA and tissue staining have proven their worth, these techniques often either require substantial amounts of starting material or are prone to high background and false negatives. The proximity ligation assay (PLA) has proven to be an exquisitely sensitive technique with very low background. Two probes that bind adjacent to one another on a protein target can be ligated, yielding a unique amplicon that can be sensitively detected by real-time PCR. We have now adapted PLA to cell surface protein targets using modified RNA aptamers, and have shown that aptamer-based cell surface PLA can successfully detect and differentiate between cells that differentially express a tumor antigen, the prostate specific membrane antigen (PSMA).
<p>Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy</p> (2019)

Despite the efficacy of the on-demand treatment for the control of acute attacks of Hereditary Angioedema due to C1-Inhibitor Deficiency (C1-INH-HAE), the number and severity of attacks and the impairment in the quality of life of the affected patients have led to the development of a new monoclonal antibody, lanadelumab, directly addressed to the blockage of bradykinin, the principal mediator of vasodilation during angioedema attacks. It is indicated for the prophylactic treatment, it is easy to administer, highly effective and with known limited side effects. The current review summarizes the development of the drug, its clinical background and its perspectives.
Dispersion-managed solitons for terrestrial transmission (1999)

We describe a scheme involving the insertion of segments of dispersion-compensating fiber, pumped to yield Raman gain, at one or more intermediate points within each 80-km-or-greater span between amplifier huts. With dispersion-managed solitons, the scheme is expected to allow for error-free, many-channel wavelength-division multiplexing, with high spectral efficiency, over transmission distances of many thousands of kilometers.
Biologic agents in the treatment of colorectal cancer: an update (2014)

SUMMARY Biologic agents are drugs that are made by living organisms. A number of these agents are now routinely used in the treatment of metastatic colorectal cancer. These biologic agents block aspects of specific signaling pathways. They are commonly presumed to have a more selective and targeted action in comparison to cytotoxic chemotherapy, although this assumption is not always borne out by data. These agents were developed with the goal of reducing the use of cytotoxic chemotherapy and thereby reducing the associated toxicities, however they are most commonly used concurrently with cytotoxics, and so the older toxicities often remain. This paper will provide a critical overview of the biologic agents that are currently used in the management of metastatic colorectal cancer, focusing on VEGF and the EGF receptor inhibitors. The rationale behind the use of these biologic agents, including the clinical trials incorporating these agents, will be discussed, and the toxicities associated with these agents will also be reviewed.