gebhart/patrepeval huggingface dataset:
ELISA for thyroglobulin in serum: recovery studies to evaluate autoantibody interference and reliability of thyroglobulin values (1996)

An ELISA for measuring thyroglobulin (Tg) in serum was developed with polyclonal antibodies to Tg on the solid phase and two monoclonal antibodies to Tg as the second antibodies. The assay has a detection limit of 1 microgram/L, a within-run imprecision (CV) of <7%, and a between-run CV of < 10%. Parallelism of the assay was shown in dilution studies, in which the percent observed/expected values for n = 5 autoantibody-containing samples gave a mean of 99% (SD 13.1 %); for n = 5 samples with undetectable autoantibody concentrations, the mean was 103% (SD 11.8%). The correlation of the ELISA with an RIA for Tg in 46 normal samples was ELISA = 1.11(RIA) + 0.52, S y/x = 2.23, SD intercept = 0.54, SD slope = 0.03, range = 0 to 53 micrograms/L, r = 0.980. Comparison of the ELISA with a reference laboratory RIA for 29 clinical samples gave a correlation of: ELISA = 1.53(RIA) - 0.48, S y/x = 9.00, SD intercept = 2.19, SD slope = 0.10, range = 0 to 98 micrograms/L, r = 0.950. To provide additional information concerning the reliability of the Tg measurement in samples containing autoantibodies to Tg, we developed a procedure for determining the percent recovery. A percent recovery greater than or equal to 80% indicates minimal interference by autoantibodies in this assay. The assay is straightforward to perform, results can be posted within 8 h, and the routinely good recovery of Tg in the presence of Tg autoantibodies indicates minimal autoantibody interference in this assay.
Effects of N alpha-tosyl-l-lysyl-chloromethylketone on the activity of cytotoxic T lymphocytes. (1980)

Abstract The lysis of allogeneic target cells by cytotoxic thymus-derived lymphocytes (CTL) was reduced markedly (20 to 100%) by an irreversible protease inhibitor, Nα-tosyl-L-lysyl-chloromethylketone (TLCK), at 0.2 to 2.0 × 10-4 M. Pretreatment of CTL and target cells indicated that TLCK affected primarily CTL, although it also decreased slightly the susceptibility of the target cells. At concentrations where TLCK blocked CTL lytic activity completely, it had no effect on the viability of the effector cell population as measured by 51Cr-label retention. In addition, the CTL treated with TLCK gradually recovered the cytotoxic activity after 1 to 4 days, suggesting that TLCK-modified components were replaced. Nε-acetyl-TLCK and Nε-succinyl-TLCK were synthesized, and they and 20 other protease inhibitors were also tested. Seventeen of the inhibitors did not block CTL activity. Whether the others had any effect could not be determined, because there was only a small difference in the concentrations at which they inhibited the cytotoxic reaction and at which they were toxic for the CTL. The overall results suggest that among the 23 inhibitors tested, TLCK was unique: it affects an unknown component, not necessarily a protease, required for cytotoxic activity of CTL. Addition of TLCK at different steps of the cytolytic sequence (conjugate formation, programming for lysis, and CTL-independent cell lysis) suggested that it affected programming for lysis, not the other steps.
Effect of DNA copy number on genetic stability of phage-displayed peptides (2004)

A small model peptide, the FLAG epitope, was cloned into two filamentous phage display vectors, f88-4 and fd88-4, creating phages f88-FLAG and fd88-FLAG, respectively. Both vectors have a gene VIII display cassette (in addition to their normal phage gene VIII) and display the cloned peptide on a few percent of the virion's 3000-4000 pVIII (major coat protein) subunits. Vector f88-4 has a replication defect and attains low DNA copy number in infected cells, while vector fd88-4 has no replication defect and attains the normal, high DNA copy number characteristic of wild-type filamentous phage. Almost no loss of displayed peptide was observed during six rounds of propagation of low copy number f88-FLAG phage. In contrast, when high copy number fd88-FLAG phage was similarly propagated, variant clones that did not display the FLAG epitope accumulated gradually. The loss of displayed peptide from the high copy number vector is undoubtedly slow enough to be overcome by even weak affinity selection, and high copy number vectors have important advantages that make their use worth considering, at least when the displayed peptides are small.
T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures. (1984)

The cytotoxic reactivity of lymphocytes for autologous melanoma cells was studied in a group of 13 melanoma patients. No cytotoxicity was observed with lymphocytes freshly isolated from peripheral blood or with lymphocytes cocultured for 7 days with autologous melanoma cells. Growth of lymphocytes previously sensitized with autologous melanoma in vitro in interleukin 2 (IL-2)-containing medium, however, resulted in cytotoxic reactivity for autologous melanoma in 7/13 patients. The reactivity of IL-2-dependent lymphocytes for autologous melanoma was particularly striking in one patient (A.V.) who has had an unexpectedly favorable clinical course and, because of their consistently high reactivity, AV lymphocytes were selected for detailed specificity analysis. After 2-3 weeks in culture in IL-2-containing medium, AV lymphocytes were cytolytic for autologous melanoma cells but not autologous Epstein-Barr virus-transformed B cells, autologous fibroblasts, or allogeneic tumor targets. Specificity of autologous melanoma reactivity was confirmed by competitive inhibition assays. The IL-2-dependent AV lymphocytes formed rosettes with sheep erythrocytes and expressed OKT 3 and Ia antigens. After longer periods of culture, AV lymphocytes were found to react with a wider range of target cells, and repeated attempts to isolate cultures with restricted reactivity to autologous melanoma by resensitization with autologous melanoma and limiting-dilution techniques were unsuccessful. The restricted reactivity of early cultures could be preserved, however, in frozen storage, but shifted again toward broader reactivity after several weeks in culture. The recognition of cytotoxic T cells with initial restricted reactivity for autologous melanoma suggests reinvestigation of the question of specific cellular immunity to human cancer.
Neuroprotection and traumatic brain injury: theoretical option or realistic proposition (2002)

Purpose of review Preclinical studies have shown that treatment to limit secondary cell damage can significantly improve outcome after traumatic brain injury. In contrast, neuroprotection trials in human traumatic brain injury have failed to convincingly demonstrate therapeutic benefit. Recent literature has begun to address this discrepancy between preclinical and clinical trials. Recent findings Perhaps the most important recent observations relate to the potential role of apoptosis in secondary brain injury. Because apoptosis peaks more than 24 h after injury, concepts about the therapeutic window for traumatic brain injury treatment have changed. Apoptosis and necrosis are in delicate balance and inhibition of one cell death pathway may enhance the other. This raises questions about the ultimate effectiveness of treatment strategies directed toward a single injury mechanism. In contrast to clinical head injury, which reflects a complex multi-factorial disorder, animal models are generally designed to address only a single injury component and are performed in genetically inbred animals of a single sex. Moreover, animal studies usually employ pretreatment or early posttreatment administration, examine moderate rather than severe injury, fail to examine brain drug levels or treatment optimization, and do not use an intent-to-treat methodology. Summary Recognition of these methodological differences between animal and human studies has led to new trial design proposals. For clinical studies, there should be better stratification of patients, a focus on moderate injury and earlier treatment, and larger sample sizes. Animal experiments should better parallel clinical studies and address therapeutic window and treatment optimization. Recognition of multiple cell death pathways should lead to new treatment strategies - including both combination drug treatment and drugs that affect multiple components of the secondary injury cascade.
Analyse expérimentale et numérique des défaillances mécaniques locales induites dans les interconnexions par les tests paramétriques et les assemblages : optimisation des procédés et des architectures des plots de connexion (2010)

The diminution of the critical dimensions in the semiconductor industry and the introduction of new brittle dielectric materials raise questions on the mechanical resistance of the die and the pad architectures. Nowadays, pad structures are prone to crack. More precisely, the electrical wafer sort (EWS), which allows checking the electrical functionality of the die, and the assemblies such as the wire bonding to achieve the electrical connections with the packaging, are performed at the wafer level and introduce high levels of local mechanical stresses. Indeed, during these operations, failures in the oxide layers of the interconnections are observed. Experimental techniques (e.g. profilometry, FIB/SEM) are developed after EWS and bonding with gold and copper wires to gain insight on the root causes and localization of the failures. Some designs of experiments are set up to evaluate the influence of the test and process parameters and also of the various pad designs on the mechanical robustness of the structures. In addition, a novel analysis procedure, based on nanoindentation technique, is employed to compare various pads, which are complex multilayer systems. Moreover, several finite element models, using both explicit and implicit schemes are developed to mimic the EWS test. Indeed, these models have shown their ability to reproduce the loading conditions, the contact between the testing needle tip and the pad, and some inertial effect during the test. Finally, a comprehensive set of tools to evaluate and optimize the pad architectures is presented. Guidelines for pad layouts are also given, providing integration insights in the frame of the technology development.
Performance of Advanced Receiver Employing Interference Rejection Combining to Suppress Inter-Cell Interference in LTE-Advanced Downlink (2011)

The interference rejection combining (IRC) receiver is effective in improving the cell-edge user throughput because it suppresses inter-cell interference. The IRC receiver is typically based on the minimum mean square error (MMSE) criteria, which requires channel estimation and covariance matrix estimation including the inter-cell interference with high accuracy. The paper investigates the gain from the IRC receiver taking into account the estimation of the interference signal, i.e., the covariance matrix, in terms of the downlink user throughput performance in a multi-cell environment. For the estimation of the covariance matrix, two estimation schemes are considered one based on data signals and the other based on the demodulation reference signal (DM-RS). In the evaluation, to assess the actual gains of the two schemes, the inter-cell interference signals from the surrounding 56 cells are actually generated in the same way as the desired signals including reference signals, and the channel propagation from all of the cells is explicitly taken into account considering pathloss, shadowing, and multipath fading. The simulation results when the inter-site distance is 500 m and the numbers of transmitter and receiver antennas are 2 and 2, respectively, show that the IRC receiver employing the covariance matrix comprising the interference and noise component estimation improves the cell-edge user throughput (defined as the 5% value in the cumulative distribution function) by approximately 22% compared to the simplified MMSE receiver that approximates the inter-cell interference as AWGN, while the IRC receiver employing the full covariance matrix estimation degrades the average user throughput due to less accurate channel and covariance matrices.
Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current. (1993)

In human myocardium, the nature of the K+ currents mediating repolarization of the action potential is still speculative. Delayed rectifier channels have recently been cloned from human myocardium, but it is unclear whether or not these currents are involved in the termination of the cardiac action potential plateau. In intact human atrial myocytes, we have identified a rapid delayed rectifier K+ current with properties and kinetics identical to those expressed by a K+ channel clone (fHK) isolated from human heart and stably incorporated into a human cell line for the first time. The myocyte current amplitude was 3.6 +/- 0.2 pA/pF (at +20 mV, n = 15) and activated with a time constant of 13.1 +/- 2 milliseconds at 0 mV (n = 15). The half-activation potential (V0.5) was -6 +/- 2.5 mV (n = 10) with a slope factor (k) of 8.6 +/- 2.2 (n = 10). The heterologously expressed fHK current amplitude was 136 pA/pF (at +20 mV, n = 9) with an activation time constant of 11.8 +/- 4.6 milliseconds at 0 mV; V0.5 was 4.1 +/- 2.4 mV (mean +/- SEM, n = 8); and k was 7.0. The conductance of single fHK channels was 16.9 picosiemens in 5 mM bath K+. Both native and cloned channel currents inactivated partially during sustained depolarizing pulses. Both currents were blocked by micromolar concentrations of 4-aminopyridine and were relatively insensitive to tetraethylammonium ions and class III antiarrhythmic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
DNA methylation in circulating tumour DNA as a biomarker for cancer. (2008)

Free circulating DNA, which is thought to be derived from the primary tumour, can be detected in the blood of patients with cancer. Detection of genetic and epigenetic alteration in this tumour DNA offers a potential source of development of prognostic and predictive biomarkers for cancer. One such change is DNA methylation of the promotor region of tumour suppressor genes. This causes down regulation of tumour suppressor gene expression, a frequent event in carcinogenesis. Hypermethylation of the promotor region of a number of genes has been detected in many tumour types and more recently these changes have been detected in circulating tumour DNA. This review will summarise the literature detailing DNA methylation in circulating tumour DNA and discuss some of the current controversies and technical challenges facing its use as a potential biomarker for cancer.
Chemistry of 2-(chloromethyl)furans. Reaction of 2-(chloromethyl)furans with aqueous potassium cyanide and other nucleophiles (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of 2-(chloromethyl)furans. Reaction of 2-(chloromethyl)furans with aqueous potassium cyanide and other nucleophilesStephen Divald, Maria C. Chun, and Madeleine M. JoullieCite this: J. Org. Chem. 1976, 41, 17, 2835–2846Publication Date (Print):August 1, 1976Publication History Published online1 May 2002Published inissue 1 August 1976https://pubs.acs.org/doi/10.1021/jo00879a010https://doi.org/10.1021/jo00879a010research-articleACS PublicationsRequest reuse permissionsArticle Views1339Altmetric-Citations40LEARN 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
The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases (2008)

Oxidative stress has been linked to the origin and progression of cardiovascular diseases. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase is a multi-component, NADPH-dependent enzyme that generates superoxide anion in the presence of molecular oxygen. The enzyme has been identified and characterized in all 3 vascular wall cell types and represents the major source of reactive oxygen species (ROS) production in the vascular wall. Inhibition of NADPH oxidase activation appears to suppress the sequence of cellular events that leads to a variety of cardiovascular diseases, including atherosclerosis. The naturally occurring methoxyphenol apocynin has been found to inhibit NADPH oxidase upon activation by peroxidases (e.g. soybean peroxidase, myeloperoxidase) or ROS under mild reaction conditions. Upon peroxidase-catalyzed activation, the apocynin oxidation products act to block the assembly and activation of NADPH oxidase. Although the mechanism of inhibition of NADPH oxidase remains largely unknown, apocynin's high effectiveness and low toxicity makes it a promising lead compound in the development of new therapeutic agents for cardiovascular diseases.
The Significance of Valine 33 as a Ligand-specific Epitope of Transforming Growth Factor α (1996)

Although binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to the EGF receptor (EGFR) is mutually competitive, their binding is not identical, and their biological activities are not always equivalent. To probe for ligand-specific interactions, we have synthesized analogues of TGFalpha with modifications to the residue lying between the fourth and fifth cysteines (the "hinge"). Although this residue lies in a structurally conserved region of the protein, it is not conserved within the EGFR ligand family. Our results show that in TGFalpha there is a preference for a bulky hydrophobic hinge residue; this contrasts with EGF, for which a hydrogen bond donor functionality is preferred. Sequence analysis of the human EGFR ligands revealed that the nature of the hinge residue correlated with the sequence in the B-loop beta-sheet. As this region is an important determinant in recognition of TGFalpha by the chicken EGFR, we assessed the mitogenicity of the TGFalpha hinge mutants, as well as the other EGFR ligands, using chicken embryo fibroblasts. The preference of the chicken EGFR for TGFalpha hinge mutants with hydrophobic side chains paralleled that of the human EGFR. Betacellulin and heparin-binding EGF-like growth factor also possess an hydrophobic hinge; both were at least as potent as TGFalpha for chicken embryo fibroblasts. EGF and amphiregulin, both with hydrogen bond donor functionalities at their hinge, displayed markedly decreased in potency by comparison with TGFalpha. We propose that EGFR ligands can be subclassified into TGFalpha-like and EGF-like and that this is of functional significance, identifying a potential mechanism whereby EGFR can discriminate between its ligands.
Phase III Multicenter Clinical Trial of the Sialyl-TN (STn)-Keyhole Limpet Hemocyanin (KLH) Vaccine for Metastatic Breast Cancer (2011)

Although STn-KLH was well tolerated in this largest to date metastatic breast cancer vaccine trial, no overall benefit in TTP or survival was observed. Lessons were learned for future vaccine study designs.
Adaptive Volterra filters for nonlinear acoustic echo cancellation. (1999)

More than 20 years ago it was shown that adaptive Volterra filters can be used for telephone echo cancellation, but the inherent need for a large number of coefficients has inhibited their practical use. Recently, first attempts have been made to combat nonlinearities in the acoustic echo path of hands-free telephones, which are caused by low-cost audio components. As these attempts are based on a memoryless nonlinear model, they are constrained to saturation effects, which can not describe the nonlinear behavior of small loudspeakers accurately enough. In this contribution, we report real time measurements with an adaptive Volterra filter. At first, we verify that loudspeaker nonlinearities encountered in the echo path of hands-free telephones have to be modelled with memory. Based on these results, we propose an adaptive Volterra filter structure with a reduced number of coefficients. The new structure is experimentally compared to echo cancellers with a memoryless nonlinear model using a real acoustic echo cancelling setup with a small loudspeaker. With the new technique, an echo reduction improvement of 7 dB over conventional linear adaptive filters is achieved. Furthermore it is shown that the proposed adaptive Volterra filter structure outperforms the memoryless approaches. 1.
Secure Execution via Program Shepherding (2002)

We introduce program shepherding, a method for monitoring control flow transfers during program execution to enforce a security policy. Program shepherding provides three techniques as building blocks for security policies. First, shepherding can restrict execution privileges on the basis of code origins. This distinction can ensure that malicious code masquerading as data is never executed, thwarting a large class of security attacks. Second, shepherding can restrict control transfers based on instruction class, source, and target. For example, shepherding can forbid execution of shared library code except through declared entry points, and can ensure that a return instruction only targets the instruction after a call. Finally, shepherding guarantees that sandboxing checks placed around any type of program operation will never be bypassed. We have implemented these capabilities efficiently in a runtime system with minimal or no performance penalties. This system operates on unmodified native binaries, requires no special hardware or operating system support, and runs on existing IA-32 machines under both Linux and Windows.