gebhart/patrepeval huggingface dataset:
Altered Metabolism (In Vivo and In Vitro) of Plasma Lipoproteins after Selective Chemical Modification of Lysine Residues of the Apoproteins (1979)

Chemical modification of lysine residues by acetoacetylation of the apoproteins of iodinated canine and human low density lipoproteins (LDL) and canine high density lipoproteins (HDL) resulted in a marked acceleration in the rate of removal of these lipoproteins from the plasma after intravenous injection into dogs. Clearance of the lipoproteins from the plasma correlated with their rapid appearance in the liver. Acetoacetylated canine (125)I-LDL (30-60% of the lysine residues modified) were essentially completely removed from the plasma within an hour, and > 75% of the activity cleared within 5 min. Reversal of the acetoacetylation of the lysine residues of the LDL restored to these lipoproteins a rate of clearance essentially identical to that of control LDL. Identical results were obtained with modified human LDL injected into dogs. At 10 min, when congruent with 90% of the acetoacetylated human (125)I-LDL had been removed from the plasma, 90% of the total injected activity could be accounted for in the liver. Furthermore, it was possible to demonstrate an enhancement in uptake and degradation of acetoacetylated LDL by canine peritoneal macrophages in vitro. The mechanism(s) responsible for the enhanced removal of the LDL and HDL in vivo and in vitro remains to be determined. By contrast, however, acetoacetylation of canine (125)I-apoE HDL(c) did not accelerate their rate of removal from the plasma but, in fact, retarded their clearance. Control (native) apoE HDL(c) were removed from the plasma (64% within 20 min) and rapidly appeared in the liver (39% at 20 min). At the same time point, only 45% of the acetoacetylated apoE HDL(c) were cleared from the plasma and <10% appeared in the liver. Acetoacetylation of the apoE HDL(c) did not enhance their uptake or degradation by macrophages. The rapid clearance from the plasma of the native apoE HDL(c) in normal and hypercholesterolemic dogs suggests that the liver may be a normal site for the removal of the cholesteryl ester-rich apoE HDL(c). The retardation in removal after acetoacetylation of apoE HDL(c) indicates that the uptake process may be mediated by a lysine-dependent recognition system.
Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacokinetics-Based Dosing Paradigms (2012)

Crohn's disease and ulcerative colitis are chronic inflammatory disorders resulting from immune dysregulation. Patients who fail conventional medical therapy require biological treatment with monoclonal antibodies (mAbs). Although mAbs are highly effective for induction and maintenance of clinical remission, not all patients respond, and a high proportion of patients lose response over time. One factor associated with loss of response is immunogenicity, whereby the production of antidrug antibodies accelerates mAb clearance. However, other factors related to patient and disease characteristics also influence the pharmacokinetics of mAbs. These factors include gender, body size, concomitant use of immunosuppressive agents, disease type, serum albumin concentration, and the degree of systemic inflammation. Because it is important to maintain clinically effective concentrations to provide optimal clinical response and drug exposure is affected by patient factors, a better understanding of the pharmacology of mAbs will ultimately result in better patient care.
Distributed meetings (2002)

The common meeting is an integral part of everyday life for most workgroups. However, due to travel, time, or other constraints, people are often not able to attend all the meetings they need to. Teleconferencing and recording of meetings can address this problem. In this paper we describe a system that provides these features, as well as a user study evaluation of the system. The system uses a variety of capture devices (a novel 360° camera, a whiteboard camera, an overview camera, and a microphone array) to provide a rich experience for people who want to participate in a meeting from a distance. The system is also combined with speaker clustering, spatial indexing, and time compression to provide a rich experience for people who miss a meeting and want to watch it afterward.
Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin (2013)

Antibodies have created high expectations for effective yet tolerated therapeutics in acute myeloid leukemia (AML). Hitherto the most exploited target is CD33, a myeloid differentiation antigen found on AML blasts in most patients and, perhaps, leukemic stem cells in some. Treatment efforts have focused on conjugated antibodies, particularly gemtuzumab ozogamicin (GO), an anti-CD33 antibody carrying a toxic calicheamicin-g 1 derivative that, after intracellular hydrolytic release, induces DNA strand breaks, apoptosis, and cell death. Serving as paradigm for this strategy, GO was the first anti-cancer immunoconjugate to obtain regulatory approval in the U.S. While efficacious as monotherapy in acute promyelocytic leukemia (APL), GO alone induces remissions in less than 25-35% of non-APL AML patients. However, emerging data from well controlled trials now indicate that GO improves survival for many non-APL AML patients, supporting the conclusion that CD33 is a clinically relevant target for some disease subsets. It is thus unfortunate that GO has become unavailable in many parts of the world, and the drug's usefulness should be reconsidered and selected patients granted access to this immunoconjugate.
Study of planarized sputter-deposited SiO2 (1978)

A theoretical model is proposed to explain the mechanism of the formation of sputter-deposited ’’planarized glass’’; a phenomenon which describes the topography change during sputter glass deposition on top of a metal strip when sufficient bias is applied to the substrate target, and the sputter-deposited ’’standard glass’’ when little or not bias is applied to the substrate target. By assuming that the deposition rate is independent of the substrate topology, and that the removal rate is a function of the slope angle of the substrate surface, it is able to explain the various experimental phenomena observed for both ’’planarized glass’’ and ’’standard glass’’. A delineation scheme is adopted to support the model by displaying the glass contour step-by-step in formation of both kinds of sputter-deposited glass.
Combination of cytosine deaminase with uracil phosphoribosyl transferase leads to local and distant bystander effects against RM1 prostate cancer in mice (2006)

We conclude that CDUPRT-GDEPT significantly suppressed the aggressive growth of RM1 prostate tumors and lung pseudo-metastases via immune mechanisms involving necrosis and apoptosis.
Kinetic studies on the reaction between native globin and haem derivatives (1960)

It was reported by Hill & Holden (1926), and confirmed by later workers, that the reaction between haematin and globin is rapid, but no numerical results appear to have been published. The reaction between peroxidase apoprotein and haematin has, however, been examined (Theorell & Maehly, 1950). It was slow, with a half-time of the order of minutes; the results with different pre- parations showed variations up to seven-fold in the rate.
Targeting c-erbB-2 expressing tumors using single-chain Fv monomers and dimers. (1995)

Single-chain Fv proteins containing a COOH-terminal cysteine (sFv') were constructed by using an antidigoxin 26.10 sFv and an anti-c-erbB-2 741F8 sFv. The fully active sFv' proteins were prepared by expression in Escherichia coli as insoluble inclusion bodies, followed by in vitro refolding using glutathione redox buffers and purification. The COOH-terminal cysteines of the refolded sFv' proteins were protected by a blocking group presumed to be the glutathionyl peptide, which was easily and selectively removed by gentle reduction. Air oxidation of the reduced sFv' monomers resulted in the efficient formation of disulfide-linked sFv' homodimers, designated (sFv')2, which were stable under oxidizing conditions and relatively slow to be disrupted under reducing conditions. The (26-10-1 sFv')-(741F8-1 sFv') heterodimer was prepared and possessed dual-antigen specificity; the active bispecific (sFv')2 dimerized under native conditions, apparently as a manifestation of self-association by the 741F8 sFv' subunit. Biodistribution and imaging studies that were performed on mice bearing human SK-OV-3 tumor xenografts that express the c-erbB-2 as a cell surface antigen were reviewed. Radioiodinated 741F8-2 (sFv')2 homodimer localized to the tumors with high specificity, as evidenced by excellent tumor:normal tissue ratios. Sagittal section autoradiography of whole animals 24 h after administration of antibody species revealed that 741F8 (sFv')2 produced a stronger tumor image than comparable doses of the 741F8 Fab, monomeric sFv', and the 26-10 (sFv')2 control without the high nonspecific background distribution of the 741F8 IgG.
Human and Simian Immunodeficiency Virus Capsid Proteins Are Major Viral Determinants of Early, Postentry Replication Blocks in Simian Cells (2002)

The cells of most Old World monkey species exhibit early, postentry restrictions on infection by human immunodeficiency virus type 1 (HIV-1) but not by simian immunodeficiency virus of macaques (SIV(mac)). Conversely, SIV(mac), but not HIV-1, infection is blocked in most New World monkey cells. By using chimeric HIV-1/SIV(mac) viruses capable of a single round of infection, we demonstrated that a major viral determinant of this restriction is the capsid (CA) protein. The efficiency of early events following HIV-1 and SIV(mac) entry is apparently determined by the interaction of the incoming viral CA and species-specific host factors.
Integration of human papillomavirus type 16 DNA sequences: a possible early event in the progression of genital tumors (1987)

The keratinocyte line SK-v harbors only integrated human papillomavirus type 16 (HPV 16) DNA sequences, although it originated from vulvar Bowenoid papules predominantly containing multiple copies of free HPV 16 genomes. We have cloned a fragment of cell DNA that contains the integrated HPV 16 DNA sequences and have shown that integration interrupts the HPV 16 genome in open reading frames E2 and L2 and creates a deletion of 813 base pairs. This allows the expression of open reading frames E6 and E7, as actually substantiated by Northern (RNA) blot analysis of SK-v RNAs with subgenomic HPV 16 RNA probes. Using a unique flanking cellular DNA sequence as the probe, we have shown that the integration of HPV 16 sequences had already occurred in the premalignant lesions from which the SK-v cell line was derived.
Solubility Temperature Dependence Predicted from 2D Structure (2015)

The objective of the study was to find a computational procedure to normalize solubility data determined at various temperatures (e.g., 10 – 50 oC) to values at a “reference” temperature (e.g., 25 °C). A simple procedure was devised to predict enthalpies of solution, ΔHsol, from which the temperature dependence of intrinsic (uncharged form) solubility, log S0, could be calculated. As dependent variables, values of ΔHsol at 25 °C were subjected to multiple linear regression (MLR) analysis, using melting points (mp) and Abraham solvation descriptors. Also, the enthalpy data were subjected to random forest regression (RFR) and recursive partition tree (RPT) analyses. A total of 626 molecules were examined, drawing on 2040 published solubility values measured at various temperatures, along with 77 direct calori metric measurements. The three different prediction methods (RFR, RPT, MLR) all indicated that the estimated standard deviations in the enthalpy data are 11-15 kJ mol-1, which is concordant with the 10 kJ mol-1 propagation error estimated from solubility measurements (assuming 0.05 log S errors), and consistent with the 7 kJ mol-1 average reproducibility in enthalpy values from interlaboratory replicates. According to the MLR model, higher values of mp, H‑bond acidity, polarizability/dipolarity, and dispersion forces relate to more positive (endothermic) enthalpy values. However, molecules that are large and have high H-bond basicity are likely to possess negative (exothermic) enthalpies of solution. With log S0 values normalized to 25 oC, it was shown that the interlaboratory average standard deviations in solubility measurement are reduced to 0.06 ‑ 0.17 log unit, with higher errors for the least-soluble druglike molecules. Such improvements in data mining are expected to contribute to more reliable in silico prediction models of solubility for use in drug discovery.
Triacylglycerol synthesis by an sn-1,2(2,3)-diacylglycerol transacylase from rat intestinal microsomes. (1993)

A membrane-associated sn-1,2(2,3)-diacylglycerol transacylase activity was purified 550-fold from the microsomes of rat intestinal villus cells. The enzyme was solubilized with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate and was isolated and purified by sequential chromatography on hydroxylapatite, an anion exchanger, Affi-Gel heparin and Cibacron blue A-agarose. SDS-polyacrylamide gel electrophoresis revealed two major closely migrating polypeptides of apparent molecular mass of 50 and 52 kDa. Incubation of the isolated enzyme with sn-1,2(2,3)dioleoyl-[2-3H]glycerol yielded trioleoyl[2-3H]glycerol and 2-oleoyl[2-3H]glycerol. The synthesis of triacylglycerols was independent of acyl-CoA, as indicated by the absence of incorporation of radioactivity from [1-14C]oleoyl-CoA into mono-, di-, or triacylglycerols under these conditions. The transacylase did not hydrolyze triacylglycerols readily and was not affected by the acyltransferase inhibitors, N-ethylmaleimide and 4,4'-diisothiocyanostilbene-2,2'-disulfonate, while the lipase/hydrolase inhibitors NaF, phenylmethylsulfonyl fluoride, and diethyl p-nitrophenyl phosphate caused partial inactivation. The enzyme was specific toward 1(3)-positions of rac 1,2-diacylglycerols but did not utilize the -1,3-diacylglycerols or other neutral lipid esters effectively and was not capable of removing fatty acids from phosphatidylcholine or of transfer of fatty acids from X (unspecified enantiomer)-1,2-diacylglycerol to lysophosphatidylcholine. Since the diacylglycerol transacylation did not lead to accumulation of either sn-1,2- or sn-2,3-diacylglycerols during incubation with the racemates, it is concluded that both sn-1,2- and sn-2,3-s are utilized at similar rates.
Site-selective cleavage of RNA by a hybrid enzyme (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSite-selective cleavage of RNA by a hybrid enzymeRonald N. Zuckermann, David R. Corey, and Peter G. SchultzCite this: J. Am. Chem. Soc. 1988, 110, 5, 1614–1615Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ja00213a040https://doi.org/10.1021/ja00213a040research-articleACS PublicationsRequest reuse permissionsArticle Views175Altmetric-Citations52LEARN 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
Specific binding of 125I-human interferon-gamma to high affinity receptors on human fibroblasts. (1982)

Highly purified human interferon-gamma (IFN-gamma) was iodinated with 125I-Bolton-Hunter reagent to a specific activity of 34 microCi/micrograms of protein. After iodination, molecular sieve chromatography was used to isolate fractions containing IFN-gamma at approximately 80-90% radioactive purity. This preparation of 125I-IFN-gamma bound specifically to high affinity binding sites on human GM-258 fibroblasts. Scatchard analysis of binding data revealed the presence of 2400 binding sites/cell, each binding with an apparent Kd of 1.5 X 10(-10) M. Binding was competitively inhibited in the presence of unlabeled IFN-gamma and, to a lesser degree, by IFN-beta, but not by IFN-alpha. Neutralizing antibodies specific for IFN-gamma efficiently inhibited the specific binding of 125I-IFN-gamma to cells. We conclude that the specific high affinity binding site is the receptor for IFN-gamma.
Cochlear micromechanics—A physical model of transduction (1980)

One of the basic questions which has persisted in the field of hearing theory is the still unresolved mechanical action of hair-cell transduction. The fundamental problem that has historically plagued researches is the discrepancy between mechanically measured tuning of basilar membrane motion and neurally measured tuning. In this paper we show that the difference between these two measures appears to be accounted for by a specific, physically motivated, micromechanical model. This model gives rise to a spectral zero which we identify as the "second-filter" of cochlear transduction. For high-frequency fibers this zero resides at a fixed frequency ratio below CF (characteristic frequency) while for fibers having low-frequency CF's the zero appears to go to zero frequency faster than CF. In this paper we first present and analyze the assumed mechanical model. We then briefly discuss a possible specific physical realization for the nonlinearity of cochlea mechanics. The nonlinear model is based on dynamical variations in outer hair cell stereocilia stiffness.
Tuning the detection wavelength of quantum-well infrared photodetectors by single high-energy implantation (2001)

Single high-energy (0.9 MeV) proton implantation and rapid thermal annealing was used to tune the spectral response of the quantum-well infrared photodetectors (QWIPs). In addition to the large redshift of the QWIPs’ response wavelength after implantation, either narrowed or broadened spectrum was obtained at different interdiffusion extent. In general, the overall device performance for the low-dose implantation was not significantly degraded. In comparison with the other implantation schemes, this single high-energy implantation is the most effective and simple technique in tuning the wavelength of QWIPs, thus, to achieve the fabrication of multicolor detectors.
Adjuvanticity (immunity-inducing property) of cord factor in mice and rats (1977)

Cord factor, a glycolipid in mycobacteria, was found to make a tolerogenic protein antigen immunogenic when injected 0 to 2 days before tolerogen injection in mice and rats. Cord factor was also found to increase phagocytic function of the reticuloendothelial system of mice, and the relationship between the immunity-inducing capacity and the phagocytic function is discussed.
EFFICIENT FLUORESCEIN SPIROLACTAM AND BIS-SPIROLACTAM SYNTHESIS (2001)

Reaction of fluorescein methyl ester at ambient temperature with a variety of amines containing different functional groups afforded a family of spirolactams, the structures of which were verified by MS, NMR, and x-ray crystallography. Bis-spirolactams were prepared by subsequent reaction of an aminospirolactam with another molecule of fluorescein methyl ester.
Anti–B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma (2020)

In this study of AMG 420 in patients with relapsed/refractory multiple myeloma, the response rate was 70%, including 50% MRD-negative complete responses, at 400 μg/d, the MTD for this study.
Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo (2005)

Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells) overexpress the transferrin receptor to increase their iron uptake, we hypothesized that iron-dependent, antimalarial drugs such as artemisinin might prove useful in treating HPV-infected or transformed cells. We tested three different artemisinin compounds and found that dihydroartemisinin (DHA) and artesunate displayed strong cytotoxic effects on HPV-immortalized and transformed cervical cells in vitro with little effect on normal cervical epithelial cells. DHA-induced cell death involved activation of the mitochondrial caspase pathway with resultant apoptosis. Apoptosis was p53 independent and was not the consequence of drug-induced reductions in viral oncogene expression. Due to its selective cytotoxicity, hydrophobicity, and known ability to penetrate epithelial surfaces, we postulated that DHA might be useful for the topical treatment of mucosal papillomavirus lesions. To test this hypothesis, we applied DHA to the oral mucosa of dogs that had been challenged with the canine oral papillomavirus. Although applied only intermittently, DHA strongly inhibited viral-induced tumor formation. Interestingly, the DHA-treated, tumor-negative dogs developed antibodies against the viral L1 capsid protein, suggesting that DHA had inhibited tumor growth but not early rounds of papillomavirus replication. These findings indicate that DHA and other artemisinin derivatives may be useful for the topical treatment of epithelial papillomavirus lesions, including those that have progressed to the neoplastic state.
Combination of signals from array coils using image‐based estimation of coil sensitivity profiles (2002)

It is well established that the optimal unbiased way to combine image data from array coils is a pixel-by-pixel sum of coil signals, with each signal weighted by the individual coil sensitivity at the location of the pixel. A pragmatic alternative combines the images from the coils as the square root of the sum of squares (SOS), which can reduce the signal-to-noise ratio (SNR) and introduce bias. This work describes how to replace coil sensitivity by an image-derived quantity that enables close to optimal signal combination up to a global intensity scaling. Typical scaling is by an individual coil sensitivity or a linear or SOS combination of the sensitivities of some or all of the coils in the array. The method decreases signal bias, improves SNR when coils have unequal noise levels, and can reduce image artifacts. It can produce phase-corrected data, which eliminates bias completely. In addition, the method allows images from arrays that include highly localized coils, such as a prostate coil and external pelvic array, to be combined with near-optimal SNR and an intensity modulation that makes them easier to view.
A novel Ecotin-Ubiquitin-Tag (ECUT) for efficient, soluble peptide production in the periplasm of Escherichia coli (2009)

This newly described method represents a useful technique for the production of authentic soluble peptides in the periplasm of E. coli. In addition, larger proteins might also be produced with the current system by the use of ubiquitin specific proteases, which can cleave off larger C-terminal extensions.