gebhart/patrepeval huggingface dataset:
In situ characterization of antigenic and functional tissue factor expression in human tumors utilizing monoclonal antibodies and recombinant factor VIIa as probes. (1994)

Tissue factor (TF), the primary initiator of blood coagulation in vivo, is expressed in vitro by a variety of cells. Previous efforts to localize TF in tissue and cells have been limited principally to the use of immunological techniques. In the present study, we describe a novel functional probe for TF expression, which can be utilized to localize functional TF in situ in human cells and tissues. This probe, a biotinylated phe-pro-arg-chloro-methyl-ketone-labeled rVIIa (FPR-ck-VIIa), interacts with TF via high-affinity binding sites. The binding of FPR-ck-VIIa, therefore, can be correlated with the ability of TF to activate clotting. In the described studies, TF antigen (TF:Ag) expression was examined immunohistochemically with various TF-specific monoclonal antibodies (MAbs) and was correlated with functional TF expression using our novel TF-binding probe (eg, FPR-ck-VIIa). Initial results indicate that TF:Ag expression correlates with the expression of functional TF (TF:VIIa), and the specificity of both types of probes was confirmed. Parallel antigenic and functional TF expression in situ was demonstrated in various human tumors. We believe this to be the first demonstration of functional TF in situ in human cells and tissues. We suggest that FPR-ck-VIIa should prove a useful reagent for studying the role of TF in the pathogenesis of clotting complications of human disease.
Direct Conversion of Tosylhydrazones to tert-Butyl Ethers under Bamford-Stevens Reaction Conditions (2001)

A new method for the preparation of tert-butyl ethers is described starting from aryl aldehyde and ketone tosylhydrazones under Bamford-Stevens reaction conditions (t-BuOK/t-BuOH).
Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein (1979)

Nonsuppressible insulin-like activity extracted and purified from human serum (NSILA-S) mimics all insulin-like effects in vitro and, after injection, in vivo in the presence of excess insulin antibodies. However, there is no evidence that it exerts acute insulin-like effects in its native form in the circulation, where it is almost completely bound to a specific large molecular weight carrier protein. In this paper we show that partially purified NSILA-S-carrier protein, devoid of endogenous insulin-like activity, inhibits the stimulatory effect of NSILA-S, but not of insulin, on 3-0-methylglucose transport and on lipogenesis from [U-(14)C]glucose in isolated rat fat cells. Concomitantly, it prevents binding of (125)I-labeled NSILA-S to the insulin receptor and to the NSILA-S-binding site. The following explanation is, therefore, offered for the absence of acute insulin-like effects of native NSILA-S in vivo: In native serum NSILA-S occurs almost exclusively as NSILA-S-carrier complex. According to recent findings the passage of this complex through blood capillaries is restricted. The present results indicate that, in addition, it is metabolically inactive, or, at least, possesses reduced metabolic activity. The well-known phenomenon that whole serum, nevertheless, exerts pronounced nonsuppressible insulin-like effects on adipose tissue in vitro seems, therefore, to be mainly caused by the presence of a large molecular weight insulin-like protein not identical to the NSILA-S-carrier complex.
Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues. (1988)

We have investigated the potential for using anti-sense non-ionic methylphosphonate oligonucleotide analogues to study the relationship between oncogene expression and maintenance of the transformed phenotype in malignant cells. Our results confirmed that the methylphosphonates are resistant to biochemical degradation and are devoid of non-specific toxicity towards cultured human HT29 cells. At low temperature (less than 5 degrees C) both N-ras anti-sense and nonsense analogue 9-mers formed 1:1 complexes in solution with an N-ras sense phosphodiester oligodeoxynucleotide 20-mer, but these were largely dissociated at 25 degrees C. Only a fraction (10-20%) of the anti-sense molecules formed stable sequence specific hybrids (Tm 34 degrees C) with the 20-mer. The biological activity of the oligonucleotide analogues was tested in cell culture at 37 degrees C using T15 cells, a line of NIH 3T3 cells transfected with multiple copies of the human N-ras oncogene under control of the glucocorticoid inducible MMTV promoter. On balance the N-ras anti-sense methylphosphonate 9-mer (20-80 microM) had no effect on these cells. In only one of five experiments was an apparent reduction in dexamethasone-induced p21N-ras protein accumulation observed in the presence of the oligonucleotide analogue. Also without effect was an anti-sense 20-mer consisting of a phosphodiester sequence bounded by two methylphosphonate linkages at each end (25-50 microM in culture media; 4.8 microM by microinjection). We conclude from these experiments that, in order to achieve pronounced effects on oncogene expression, it may be necessary to use longer anti-sense methylphosphonate chains, affinity purified for their ability to hybridize with the target sequences.
Amperometric Electrochemical Microsystem for a Miniaturized Protein Biosensor Array (2009)

Protein-based bioelectrochemical interfaces offer great potential for rapid detection, continuous use, and miniaturized sensor arrays. This paper introduces a microsystem platform that enables multiple bioelectrochemical interfaces to be interrogated simultaneously by an onchip amperometric readout system. A post-complementary metal-oxide semiconductor (CMOS) fabrication procedure is described that permits the formation of planar electrode arrays and self assembly of biosensor interfaces on the electrodes. The onchip, 0.5-mum CMOS readout electronics include a compact potentiostat that supports a very broad range of input currents-6 pA to 10 muA-to accommodate diverse biosensor interfaces. The 2.3 times 2.2-mm chip operates from a 5-V supply at 0.6 mA. A prototype electrochemical sensor platform, including an onchip potentiostat and miniaturized biosensor array, was characterized by using cyclic voltammetry. The linear relationship between the oxidization peak values and the concentrations of target analytes in the solution verifies functionality of the system and demonstrates the potential for future implementations of this platform in high sensitivity, low cost, and onchip protein-based sensor arrays.
Nuclear-Cytoplasmic Partitioning of Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) Differentially Regulates the Cell Cycle and Apoptosis (2005)

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor phosphatase that dephosphorylates both protein and lipid substrates, is found to be mutated in both heritable and sporadic breast cancer. Cellular PTEN has been shown to regulate Akt phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, p27(kip1), and cyclin D1 protein levels. Additionally, we and others have shown that PTEN can regulate not only the cell cycle but also cellular apoptosis. Until recently, the functions of PTEN have been thought to occur through cytoplasmic PTEN. However, we have shown that PTEN localizes to the nucleus and that this localization coincides with the G0-G1 phases of the cell cycle. Furthermore, we have shown that PTEN has bipartite nuclear localization sequence (NLS)-like sequences that are required for major vault protein-mediated nuclear import. These findings suggest that subcellular localization of PTEN may regulate its function and that nuclear-localized PTEN may regulate unique cellular functions that have been attributed to cytoplasmic PTEN. To examine this possibility, we analyzed downstream PTEN readouts using MCF-7 Tet-Off breast cancer cell lines stably transfected with two different NLS mutant PTEN constructs, which do not localize to the nucleus, and compared these with cells transfected with wild-type PTEN and empty vector control cells. We found that cytoplasmic PTEN down-regulates phosphorylation of Akt and up-regulates p27(kip1), whereas nuclear PTEN down-regulates cyclin D1 and prevents the phosphorylation of MAPK. Additionally, whereas we observe that nuclear PTEN is required for cell cycle arrest, we found that cytoplasmic PTEN is required for apoptosis. Our observations show that nuclear-cytoplasmic partitioning differentially regulates the cell cycle and apoptosis and, in this manner, provide further evidence that nuclear import of PTEN should play a role in carcinogenesis.
Improved circulating half-life and efficacy of an antibody-interleukin 2 immunocytokine based on reduced intracellular proteolysis. (2002)

We have identified modifications that dramatically improve the circulating half-life of immunocytokines based on increased resistance to intracellular degradation and thus have demonstrated how these molecules can be recycled in and out of an intracellular compartment. Use of these improved immunocytokines with highly favorable pharmacokinetic properties and retained effector functions should lead to more effective treatment of epithelial cancers.
Genetic Perspectives on Human Origins and Differentiation (2000)

This is a review of genetic evidence about the ancient demography of the ancestors of our species and about the genesis of worldwide human diversity. The issue of whether or not a population size bottleneck occurred among our ancestors is under debate among geneticists as well as among anthropologists. The bottleneck, if it occurred, would confirm the Garden of Eden (GOE) model of the origin of modern humans. The competing model, multiregional evolution (MRE), posits that the number of human ancestors has been large, occupying much of the temperate Old World for the last two million years. While several classes of genetic marker seem to contain a strong signal of demographic recovery from a small number of ancestors, other nuclear loci show no such signal. The pattern at these loci is compatible with the existence of widespread balancing selection in humans. The study of human diversity at (putatively) neutral genetic marker loci has been hampered since the beginning by ascertainment bias since they were discovered in Europeans. The high levels of polymorphism at microsatellite loci means that they are free of this bias. Microsatellites exhibit a clear almost linear diversity gradient away from Africa, so that New World populations are approximately 15% less diverse than African populations. This pattern is not compatible with a model of a single large population expansion and colonization of most of the Earth by our ancestors but suggests, instead, gradual loss of diversity in successive colonization bottlenecks as our species grew and spread.
Low-cost amorphous silicon-based 160x120 uncooled microbolometer 2D array for high-volume applications (2004)

Uncooled infrared focal plane arrays are being developed for a wide range of thermal imaging applications. Developments are focused on the improvement of their sensitivity enabling the possibility of reducing the pixel pitch in order to decrease the total system (size and weight) by using smaller optics. The amorphous silicon technology is the latest one developed by CEA / LETI and transferred to ULIS to manufacture 160 x 120 2D arrays. We developed for this device a low cost package based on existing technologies. This device is well adapted to high volume process control applications where spatial resolution (in terms of pixel number) is less important than device costs.
CT Colonography Using 360° Virtual Dissection: A Feasibility Study (2005)

Although distortion of colonic structures exists at virtual dissection, it does so in recognizable patterns, so that sensitivity for polyp detection is not compromised.
Phase 1/2 dose‐escalation study of a GM‐CSF‐secreting, allogeneic, cellular immunotherapy for metastatic hormone‐refractory prostate cancer (2008)

This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway.
Development of a Custom High-Throughput Preparative Liquid Chromatography/Mass Spectrometer Platform for the Preparative Purification and Analytical Analysis of Compound Libraries (2003)

Solution-phase parallel synthesis has had a profound impact on the speed of compound synthesis delivering relatively pure compounds (>80%) in short order. However, to develop structure activity relationships (SAR) for a compound series, each library member should preferably be >95% pure. Historically, achieving and quantifying such high-purity criteria for each library member proved to be the slow step for most lead discovery groups. To address this issue, significant modifications have been made to a commercial Agilent preparative LC/MS system to allow for the general mass-guided purification of diverse compound libraries. The custom modifications include (1) the "DMSO slug" approach for the purification of samples with poor solubility; (2) an active splitter to reduce system back-pressure, reduce the delay volume, and allow for a variable split ratio; (3) a sample loading pump for the quick purification of large, dilute samples; (4) a preparative column-selection valve to quickly change column selectivity or sample loading; and (5) an analytical injector with a separate flow path for crude reaction or fraction analyses.
Circumventing immunogenicity in the development of therapeutic antibodies. (2009)

The development of anti-therapeutic antibody immune responses can limit efficacy and reduce the safety of antibody treatments. Despite significant advances to minimize such immune responses, these responses still occur, even against fully human antibodies. Thus, the ability to assess the immunogenic potential of a therapeutic antibody can provide significant benefits during the development cycle of a therapeutic protein, and may lead to the future development of therapeutic antibodies that possess minimal immunogenicity. In particular, in vitro, in silico and ex vivo methods have been developed for the prediction of T-cell epitopes that can lead to immunogenicity. Ultimately, immunogenicity may be completely avoided by the generation of humanized or fully human non-immunogenic therapeutic antibodies using techniques such as deimmunization and composite human antibodies.
Phosphofructokinases from Escherichia coli. Purification and characterization of the nonallosteric isozyme. (1978)

The main phosphofructokinase of Escherichia coli (PFK I) is an extensively studied allosteric enzyme specified by the pfkA gene. A nonallosteric phosphofructokinase was reported (Fraenkel, D.G., Kotlarz, D., and Bluc, H. (1973) J. Biol. Chem. 248, 4865-4866) in strains carrying the pfkB1 mutation, a suppressor of pfkA mutants, and very low levels of this enzyme have also been detected in strains not carrying the suppressor (i.e. pfkB+). The nonallosteric protein has now been prepared pure from three strains, one carrying pfkB1 and pfkA+, one carrying pfkB1 and completely deleted for pfkA, and one carrying pfkB+ and also deleted for pfkA. It is apparently the same enzyme (PFK II) in all three strains, which shows that pfkB1 is a mutation affecting the amount of a normally minor isozyme. PFK II is a tetramer of slightly larger subunit molecular weight than PFK I (36,000 and 34,000, respectively). No immunological cross-reactivity was detected between PFK II and PFK I. Unlike PFK I, PFK II does not show cooperative interactions with fructose-6-P, inhibition by P-enolpyruvate, or activation by ADP. Also unlike PFK I, PFK II is somewhat sensitive to inhibition by fructose-1,6-P2 and can use tagatose-6-P as substrate. Both enzymes can perform the reverse reaction, fructose-6-P + ATP from fructose-1,6-P2 + ADP in vitro, but not in vivo. The normal function of PFK II is not known.
Infrequency of isolation of HTLV-III virus from saliva in AIDS [letter] (1985)

The acquired immunodeficiency syndrome (AIDS) is a sexually transmitted disease that can also be transmitted through contaminated blood or blood products. This fact is supported in part by the recovery of human T-cell lymphotropic virus Type III (HTLV-III) the etiologic agent of AIDS from blood and semen. However the report of HTLV-III isolation from the saliva of infected patients has raised concern about the possible casual transmission of this virus although epidemiologic studies have not supported casual contagion. In the past 12 months we have attempted to isolate HTLV-III from 83 saliva samples from 71 homosexual men seropositive for HTLV-III who were studied at the Massachusetts General Hospital. All saliva specimens were cultured within 60 minutes after collection. In addition blood was also obtained from 50 of the 71 men for virus isolation. Our results are summarized in Table I. 1 of 83 saliva specimens was positive for HTLV-III whereas 28 of 50 blood cultures (56%) yielded the virus. The virus-positive saliva (unfiltered) was obtained from a patient with AIDS who had pneumocystis pneumonia candidal esophagitis and thrush. His saliva culture demonstrated reverse transcriptase activity only after 21 days in culture. In contrast his blood culture showed reverse transcriptase activity on day 3. This suggests that the HTLV-III titer of this patients saliva was substantially less than that of his blood. The infrequent isolation of HTLV-III from saliva reported here is unlikely to be due to improper methods because our isolation rate from the blood of infected persons is comparable to those reported by other laboratories. In addition we have had little difficulty in recovering the virus from the cerebrospinal fluid and neural tissues of HTLV-III-infected patients with neurologic dynfunction. Therefore we conclude that HTLV-III is present infrequently in the saliva of infected persons. When it was detected in the saliva of 1 patient with intraoral disease the amount of virus present was small. These findings are consistent with epidemiologic data indicating the casual transmission of HTLV-III does not occur even among household members exposed to the saliva of infected persons. These results may be useful in allaying public concern regarding the casual spread of AIDS and HTLV-III infection. (full text)
Delivery of NGF to the Brain: Intranasal versus Ocular Administration in Anti-NGF Transgenic Mice (2009)

Nerve growth factor (NGF) has a great potential for the treatment of Alzheimer's disease. However, the therapeutic administration of NGF represents a significant challenge, due to the difficulty to deliver relevant doses to the brain, in a safe and non-invasive way. We previously demonstrated the efficacy of a non-invasive delivery of NGF to the brain in animal models, by an intranasal route. Recently, topical eye application of NGF was proposed, as an option for the delivery of NGF to the brain. Here, we compare the efficacy of the two delivery routes of hNGF-61, a recombinant traceable form of human NGF, in the mouse neurodegeneration model AD11. The intranasal administration appeared to be significantly more effective than the ocular one, in rescuing the neurodegenerative phenotypic hallmarks in AD11 mice. The ocular administration of hNGF-61 showed a more limited efficacy, even at higher doses. Thus, NGF nasal drops represent a viable and effective option to successfully deliver therapeutic NGF to the brain in a non-invasive manner.
Synthese und biologische Aktivität von α‐Methylen‐γ‐butyrolactonen (1985)

Abstract α‐Methylen‐γ‐butyrolactone [Dihydro‐3‐methylen‐2(3 H )furanone] bilden eine wichtige Gruppe von Naturstoffen und haben vielseitige biologische Aktivitäten. Fortschritte in der Synthese des Heterocyclus sowie die Klassifizierung der Synthesemethoden sind nicht nur von praktischem Interesse, sondern auch grundsätzlich wichtig als aktuelles Beispiel für den Aufbau von Verbindungen mit der ungewöhnlichen 1,4‐Anordnung der funktionellen Gruppen sowie einer Nucleophil‐empfindlichen α‐substituierten Acrylester‐Einheit.
An Open Approach to Autonomous Vehicles (2015)

Autonomous vehicles are an emerging application of automotive technology. They can recognize the scene, plan the path, and control the motion by themselves while interacting with drivers. Although they receive considerable attention, components of autonomous vehicles are not accessible to the public but instead are developed as proprietary assets. To facilitate the development of autonomous vehicles, this article introduces an open platform using commodity vehicles and sensors. Specifically, the authors present algorithms, software libraries, and datasets required for scene recognition, path planning, and vehicle control. This open platform allows researchers and developers to study the basis of autonomous vehicles, design new algorithms, and test their performance using the common interface.
Attempted synthesis of a keto diazene: reactions of propargylic amines, sulfamides, and ureas (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAttempted synthesis of a keto diazene: reactions of propargylic amines, sulfamides, and ureasSai Keung Chiu, Michael Dube, Leonard Keifer, Sandor Szilagyi, and J. W. TimberlakeCite this: J. Org. Chem. 1978, 43, 1, 61–65Publication Date (Print):January 1, 1978Publication History Published online1 May 2002Published inissue 1 January 1978https://pubs.acs.org/doi/10.1021/jo00395a015https://doi.org/10.1021/jo00395a015research-articleACS PublicationsRequest reuse permissionsArticle Views386Altmetric-Citations15LEARN 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
Editorial: Mechanisms of neuroinflammation and inflammatory neurodegeneration in acute brain injury (2015)

EDITORIAL article Front. Cell. Neurosci., 05 August 2015Sec. Non-Neuronal Cells Volume 9 - 2015 | https://doi.org/10.3389/fncel.2015.00300
Methods to Engineer and Identify IgG1 Variants with Improved FcRn Binding or Effector Function (2012)

Antibodies as therapeutic agents have gained broad acceptance as shown by the number of antibodies in clinical use and many more in clinical development. This utility is an outcome of the high specificity and affinity of the antigen-binding site comprised of the heavy and light chain variable domains. In addition, the Fc portion of human or humanized IgG(1) antibodies promotes long half-life through interaction with the recycling FcRn receptor and effects killing functions through interaction with complement and Fcγ receptors. Engineering the Fc portion to increase half-life through stronger binding to FcRn, or to increase complement or cell-mediated killing may lead to improved therapeutic antibodies. These improvements may benefit the patients through convenience in dosing or increased efficacy. Here we describe protocols for generating Fc-engineered IgG(1) antibodies and assays to measure Fc receptor binding, antibody dependent cellular cytotoxicity activity, and complement dependent cytotoxicity activity to identify variants with improved FcRn binding or effector function.