gebhart/patrepeval huggingface dataset:
Cancer therapeutic antibodies come of age: Targeting minimal residual disease (2007)

Ten years after the first clinical application of Rituximab, an anti-CD20 recombinant monoclonal antibody, immunotherapy has become common practice in oncology wards. Thanks to the great diversity of the immune system and the powerful methodology of genetic engineering, the pharmacologic potential of antibody-based therapy is far from exhaustion. The recent application of Trastuzumab, an antibody to a receptor tyrosine kinase, in adjuvant breast cancer therapy marks the beginning of a new phase in cancer treatment. Here we discuss molecular mechanisms of antibody-based therapy, the emerging ability to target minimal disease and the therapeutic potential of combining antibodies with other modalities.
Five‐year followup of rheumatoid arthritis patients after early treatment with disease‐modifying antirheumatic drugs versus treatment according to the pyramid approach in the first year (2003)

The clinical results in favor of the early DMARD group, as observed after the first year, were not as evident after 5 years. This indicates that a more aggressive treatment approach in early RA is required, and that treatment should be continued for a prolonged period of time, in order to maintain the advantages obtained in the first year.
Pre-induction of Anesthesia in Pediatric Patients with Nasally Administered Sufentanil (1988)

To evaluate nasally administered sufentanil, 1.5-4.5 micrograms/kg, for pre-induction (i.e., pre-medication/induction) of anesthesia in pediatric patients, the authors studied ASA PS 1 or 2 patients scheduled for elective surgery. Eighty children, ages 6 months to 7 yr, were randomized to receive sufentanil (1.5, 3.0, or 4.5 micrograms/kg) or placebo (normal saline, 0.03 ml/kg) nasally over 15-20 s. Induction of anesthesia was completed with 5% halothane and O2 via facemask. After tracheal intubation, anesthesia was maintained with N2O (60-70%) and halothane, as clinically indicated. A blinded observer remained with the child from prior to drug administration until discharge from the recovery room. Patients given sufentanil were more likely to separate willingly from their parents and be judged as calm at or before 10 min compared to those given saline. Ventilatory compliance during induction of anesthesia decreased markedly in 25% of subjects given sufentanil, 4.5 micrograms/kg. Subjects given sufentanil moved or coughed less during tracheal intubation and required less halothane compared to those given placebo. During recovery, patients given sufentanil cried less and fewer needed analgesics; recovery times were similar for all groups. However, patients given sufentanil, 4.5 micrograms/kg, had a higher incidence of vomiting in the recovery room and during the first postoperative day. The authors conclude that nasally administered sufentanil, 1.5 or 3.0 micrograms/kg, facilitates separation of children from parents, has minimal side effects, may improve intubating conditions, and can provide postoperative analgesia.
Stages of Polymyxin B Interaction with the Escherichia coli Cell Envelope (2000)

The effects of polymyxin B (PMB) on the Escherichia coli outer (OM) and cytoplasmic membrane (CM) permeabilities were studied by monitoring the fluxes of tetraphenylphosphonium, phenyldicarbaundecaborane, and K(+) and H(+) ions. At concentrations between 2 and 20 microgram/ml, PMB increased the OM permeability to lipophilic compounds and induced a leakage of K(+) from the cytosol and an accumulation of lipophilic anions in the cellular membranes but did not cause the depolarization of the CM. At higher concentrations, PMB depolarized the CM, forming ion-permeable pores in the cell envelope. The permeability characteristics of PMB-induced pores mimic those of bacteriophage- and/or bacteriocin-induced channels. However, the bactericidal effect of PMB took place at concentrations below 20 microgram/ml, indicating that this effect is not caused by pore formation. Under conditions of increased ionic strength, PMB made the OM permeable to lipophilic compounds and decreased the K(+) gradient but was not able to depolarize the cells. The OM-permeabilizing effect of PMB can be diminished by increasing the concentration of Mg(2+). The major new findings of this work are as follows: (i) the OM-permeabilizing action of PMB was dissected from its depolarizing effect on the CM, (ii) the PMB-induced ion-permeable pores in bacterial envelope were registered, and (iii) the pore formation and depolarization of the CM are not obligatory for the bactericidal action of PMB and dissipation of the K(+) gradient on the CM.
Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates. (1985)

Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis.
Applications of the Priz light modulator (1982)

The Priz light modulator suppresses input data at zero spatial frequency, can provide directional spatial filtering, and can perform dynamic image selection or change detection. In this paper, we summarize the Priz's performance and provide experimental confirmation of the above three image processing applications of this device.
Optimal Design of Wireless Power Transmission Links for Millimeter-Sized Biomedical Implants (2015)

This paper presents a design methodology for RF power transmission to millimeter-sized implantable biomedical devices. The optimal operating frequency and coil geometries are found such that power transfer efficiency (PTE) and tissue-loss-constrained allowed power are maximized. We define receiver power reception susceptibility (Rx-PRS) and transmitter figure of merit (Tx-FoM) such that their multiplication yields the PTE. Rx-PRS and Tx-FoM define the roles of the Rx and Tx in the PTE, respectively. First, the optimal Rx coil geometry and operating frequency range are identified such that the Rx-PRS is maximized for given implant constraints. Since the Rx is very small and has lesser design freedom than the Tx, the overall operating frequency is restricted mainly by the Rx. Rx-PRS identifies such operating frequency constraint imposed by the Rx. Secondly, the Tx coil geometry is selected such that the Tx-FoM is maximized under the frequency constraint at which the Rx-PRS was saturated. This aligns the target frequency range of Tx optimization with the frequency range at which Rx performance is high, resulting in the maximum PTE. Finally, we have found that even in the frequency range at which the PTE is relatively flat, the tissue loss per unit delivered power can be significantly different for each frequency. The Rx-PRS can predict the frequency range at which the tissue loss per unit delivered power is minimized while PTE is maintained high. In this way, frequency adjustment for the PTE and tissue-loss-constrained allowed power is realized by characterizing the Rx-PRS. The design procedure was verified through full-wave electromagnetic field simulations and measurements using de-embedding method. A prototype implant, 1 mm in diameter, achieved PTE of 0.56% ( -22.5 dB) and power delivered to load (PDL) was 224 μW at 200 MHz with 12 mm Tx-to-Rx separation in the tissue environment.
Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. (1992)

The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hCG alpha and hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and specifically identified nonseminomatous testicular tumors. Significant serum elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of cancer patients, normal individuals, and disease controls. In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical carcinomas. All normal subjects and disease controls had free hCG beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of malignancy in general and specifically defines a subgroup of aggressive nongonadal malignancies.
Comprehensive US government program for dried plasma development (2016)

Transfusion of plasma early after severe injury has been associated with improved survival. There are significant logistic factors that limit the ability to deliver plasma where needed in austere environments, such as the battlefield or during a significant civilian emergency. While some countries have access to more logistically supportable dried plasma, there is no such product approved for use in the United States. There is a clear need for a Food and Drug Administration (FDA)-approved dried plasma for military and emergency-preparedness uses, as well as for civilian use in remote or austere settings. The Department of Defense (DoD) and Biomedical Advanced Research and Development Authority are sponsoring development of three dried plasma products, incorporating different technologic approaches and business models. At the same time, the DoD is sponsoring prospective, randomized clinical studies on the prehospital use of plasma. These efforts are part of a coordinated program to provide a dried plasma for military and civilian applications and to produce additional information on plasma use so that, by the time we have an FDA-approved dried plasma, we will better understand how to use it.
Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study (2014)

This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.
Seven-membered heterocycles. VI. 4-Alkylidene-1-benzothiepin-5(2H)-ones and the reaction of halogenated 3,4-dihydro-1-benzothiepin-5(2H)-ones with base (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSeven-membered heterocycles. VI. 4-Alkylidene-1-benzothiepin-5(2H)-ones and the reaction of halogenated 3,4-dihydro-1-benzothiepin-5(2H)-ones with baseVincent J. Traynelis, John C. Sih, and Dan M. BorgnaesCite this: J. Org. Chem. 1973, 38, 15, 2629–2637Publication Date (Print):July 1, 1973Publication History Published online1 May 2002Published inissue 1 July 1973https://pubs.acs.org/doi/10.1021/jo00955a012https://doi.org/10.1021/jo00955a012research-articleACS PublicationsRequest reuse permissionsArticle Views56Altmetric-Citations14LEARN 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
Distribution of peroxidase and granulocytes in the human uterus. (1986)

A variety of uterine cell types demonstrate endogenous peroxidase activity. Ultracytochemical localization, biochemical assays, and uterine granulocyte counts were used to characterize peroxidase activity in various regions of the human uterus and cervix during the menstrual cycle and during the postmenopausal period. Previous studies of rat uteri, using electron microscopy and biochemical assays, have shown that endometrial peroxidase is induced by estrogenic stimulation (Anderson, De Sombre, and Kang, J Cell Biol 64:668, 1975; and Biol Reprod 16:409, 1977). Tissue samples from four regions of the human uterus and one sample from the endocervix were processed for ultrastructural cytochemistry, biochemical assay, and histology. Endogenous peroxidase activity was identified with electron microscopy in the endoplasmic reticulum of endometrial epithelial cells lining four regions of the uterine cavity; the isthmus, body (2), and fundus, of some proliferative phase (2 of 6), all secretory phase (4 of 4) and all postmenopausal (3 of 3) endometria. Peroxidase activity was not demonstrable in endocervical epithelial cells. Endogenous peroxidase activity was also identified in the cytoplasmic granules of uterine eosinophils and neutrophils and in the endoplasmic reticulum of mast cells. These uterine granule-containing cells, identified with special stains in the histologic sections, were quantitated. Approximately 80% of these "uterine granulocytes" from normal uteri without intrauterine devices were neutrophils. In women of reproductive age the uterine granulocytes, although present throughout the menstrual cycle, were most numerous in the endocervix and lower uterine segment. The highest biochemical assays of peroxidase activity were also obtained in the cervix and lower uterine segment. Uterine granulocyte counts varied directly with biochemical assays of peroxidase activity indicating that they were a major determinant of biochemical peroxidase activity. Endometrial epithelial peroxidase is anatomically and temporally well placed to function as an important adjunct in maintaining a mucosal barrier to microorganisms.
The Effects of Electrode‐Tissue Contact on Radiofrequency Lesion Generation (1997)

During the generation of radiofrequency (RF) lesions in the ventricular myocardium, the maintenance of adequate electrode-tissue contact is critically important. In this study, lesion dimensions and temperature and impedance changes were evaluated while controlling electrode-tissue contact levels (-5, 0, +1, and +3 mm) and power levels (10, 20, and 30 W). This data was used to assess the ability of impedance and temperature monitoring to provide useful information about the quality of electrode-tissue contact. The results show that as the electrode-tissue contact increases, so does the amount of temperature rise. With the electrode floating in blood (-5 contact), the average maximum temperature increase with 20 and 30 W was only 7 +/- 1 and 11 +/- 2 degrees C, respectively. At 20 and 30 W the temperature plateaued shortly after the initiation of power application. With good electrode-tissue contact (+1 mm or +3 mm), the temperature increase within the first 10 seconds was significantly greater than the temperature increase from baseline with poor contact (0 mm or -5 mm) and reached a maximum of 60 +/- 1 degrees C after 60 seconds of power application. As the electrode-tissue contact increased, so did the rate and level of impedance decrease. However, the rate of impedance decrease was slower compared to the rate of temperature rise. With the electrode floating in blood, the maximum impedance decreases with 20 and 30 W were 6 +/- 6 omega and 9 +/- 5 omega, respectively. The impedances plateaued after a few seconds of power application. With the electrode in good contact, the maximum impedance decreases with 20 and 30 W were 25 +/- 2 omega and 20 +/- 6 omega, respectively. In these cases the rate of the impedance decrease plateaued after 40 seconds of power application. The increase in lesion diameter and depth correlate well with decreasing impedance and increasing temperature. However, lesion depth appears to correlate better with impedance than temperature. We conclude that, since the electrode-tissue contact is not known prior to the application of power to the endocardium, in the absence of a temperature control system, the power should initially be set at a low level. The power should be increased slowly over 20-30 seconds, and then maintained at its final level for at least 90 seconds to allow for maximal lesion depth maturation. The power level should be lowered if the impedance drop exceeds 15 omega.
Apoptosis induced by HIV infection in H9 T cells is blocked by ICE-family protease inhibition but not by a Fas(CD95) antagonist (1996)

Infection of human CD4-positive T lymphocytes by human immunodeficiency virus type 1 (HIV-1) is thought to lead to death of infected cells by apoptosis, although one recent report questions this conclusion. Here we demonstrate that HIV-1-induced apoptosis of the H9 human T cell line is blocked by peptide inhibitors of IL-1 beta converting enzyme (ICE)-family proteases, but not by the antagonistic M3 anti-Fas Ab. Apoptosis occurred in all phases of the cell cycle, not selectively in G2 as a consequence of vpr-mediated cell cycle arrest. We conclude that apoptosis accounts for all cell death related to HIV-1 infection of the human CD4-positive cell line H9, requires an ICE-like protease but is not Fas mediated, and occurs in all phases of the cell cycle.
A Bispecific Antibody-Based Approach for Targeting Mesothelin in Triple Negative Breast Cancer (2019)

Triple negative breast cancers (TNBC) remain a major medical challenge due to poor prognosis and limited treatment options. Mesothelin is a glycosyl-phosphatidyl inositol-linked membrane protein with restricted normal expression and high level expression in a large proportion of TNBC, thus qualifying as an attractive target. Its overexpression in breast tumors has been recently correlated with a decreased disease-free survival and an increase of distant metastases. The objective of the study was to investigate the relevance of a bispecific antibody-based immunotherapy approach through mesothelin targeting and CD16 engagement using a Fab-like bispecific format (MesobsFab). Using two TNBC cell lines with different level of surface mesothelin and epithelial/mesenchymal phenotypes, we showed that, <i>in vitro</i>, MesobsFab promotes the recruitment and penetration of NK cells into tumor spheroids, induces potent dose-dependent cell-mediated cytotoxicity of mesothelin-positive tumor cells, cytokine secretion, and decreases cell invasiveness. MesobsFab was able to induce cytotoxicity in resting human peripheral blood mononuclear cells (PBMC), mainly through its NK cells-mediated antibody dependent cell cytotoxicity (ADCC) activity. <i>In vivo</i>, the anti-tumor effect of MesobsFab depends upon a threshold of MSLN density on target cells. Collectively our data support mesothelin as a relevant therapeutic target for the subset of TNBC that overexpresses mesothelin characterized by a low overall and disease-free survival as well as the potential of MesobsFab as antibody-based immunotherapeutics.
8. Adaptive Mesh Refinement Strategies (2002)

This chapter describes a local projection technique (analogous to that given in Chapter 5.3) for a two-dimensional case. We demonstrate that this projection technique, which provides improved state gradient approximations, can be combined with adaptive grid refinement, on both the state and sensitivities, to improve the accuracy of sensitivity approximations. A case study is presented to evaluate the use of state and sensitivity approximations for the evaluation of cost functionals and their gradients in optimization. 8.1 A Local Projection for Higher Dimensions In this section, we describe the local projection scheme employed in the error estimation module of the finite element code described in Chapter 7. This local projection scheme is virtually the same as the local scheme for the one-dimensional model problem discussed in section 5.3.2, yet it is presented for a two-dimensional problem below since the use of higher-order finite elements in higher dimensions adds some complexities not previously discussed. Again, the local projection scheme involves performing a series of projections on subdomains of Ω. The projected gradients are given as polynomial expansions around a given vertex, ξi, of a finite element mesh. The subdomain, Ωξi, over which the projection is defined consists of all elements having ξi = (xi, yi) as a vertex. Figure 8.1 illustrates a typical subdomain, a finite element mesh of quadratic triangles. In principle, the choice of the degree of the polynomial expansion for the improved gradient approximation is independent of the selection of the finite element basis being used. However, in practice, the degree of the polynomial expansion is chosen to match the degree of the finite element basis employed. This leads to an order of accuracy improvement in the gradient approximations. For all the numerical results presented in section 8.2 below, quadratic triangular finite elements were used and so the locally projected gradients are written as polynomials of degree two on Ωξi. At element vertices, ξ1, ξ2, and ξ3, we define g* to be the local least-squares projection of the finite element derivative, ∇uh, onto the space of quadratic polynomials. For ease of notation, we denote ∇uh by gh.