gebhart/patrepeval huggingface dataset:
Rapid whole monoclonal antibody analysis by mass spectrometry: An Ultra scale‐down study of the effect of harvesting by centrifugation on the post‐translational modification profile (2010)

With the trend towards the generation and production of increasing numbers of complex biopharmaceutical (protein based) products, there is an increased need and requirement to characterize both the product and production process in terms of robustness and reproducibility. This is of particular importance for products from mammalian cell culture which have large molecular structures and more often than not complex post-translational modifications (PTMs) that can impact the efficacy, stability and ultimately the safety of the final product. It is therefore vital to understand how the operating conditions of a bioprocess affect the distribution and make up of these PTMs to ensure a consistent quality and activity in the final product. Here we have characterized a typical bioprocess and determined (a) how the time of harvest from a mammalian cell culture and, (b) through the use of an ultra scale-down mimic how the nature of the primary recovery stages, affect the distribution and make up of the PTMs observed on a recombinant IgG(4) monoclonal antibody. In particular we describe the use of rapid whole antibody analysis by mass spectrometry to analyze simultaneously the changes that occur to the cleavage of heavy chain C-terminal lysine residues and the glycosylation pattern, as well as the presence of HL dimers. The time of harvest was found to have a large impact upon the range of glycosylation patterns observed, but not upon C-terminal lysine cleavage. The culture age had a profound impact on the ratio of different glycan moieties found on antibody molecules. The proportion of short glycans increased (e.g., (G0F)(2) 20-35%), with an associated decrease in the proportion of long glycans with culture age (e.g., (G2F)(2) 7-4%, and G1F/G2F from 15.2% to 7.8%). Ultra scale-down mimics showed that subsequent processing of these cultures did not change the post-translational modifications investigated, but did increase the proportion of half antibodies present in the process stream. The combination of ultra scale-down methodology and whole antibody analysis by mass spectrometry has demonstrated that the effects of processing on the detailed molecular structure of a monoclonal antibody can be rapidly determined early in the development process. In this study we have demonstrated this analysis to be applicable to critical process design decisions (e.g., time of harvest) in terms of achieving a desired molecular structure, but this approach could also be applied as a selection criterion as to the suitability of a platform process for the preparation of a new drug candidate. Also the methodology provides means for bioprocess engineers to predict at the discovery phase how a bioprocess will impact upon the quality of the final product.
The Size and Sequence Organization of the Centromeric Region of Arabidopsis thaliana Chromosome 5 (2000)

We have determined the size of the centromeric region of Arabidopsis thaliana chromosome 5, which corresponds to the genetically defined centromere by Copenhaver et al. (Science, 286, 2468-2474, 1999) on the basis of restriction analysis. As a large clone gap was present in the previously constructed contig map of the centromeric region, the restriction map of this region was constructed using Asc I, Not I, Apa I and Pme I and genomic DNA from a hypomethylated strain. The size of the centromeric region finally estimated by combination with the sequence data of cloned regions at both sides was 4.35 megabases (Mb). This value is over 2 Mb longer than those estimated in our previous work and also by Copenhaver et al. Combing this centromeric region with the physical map previously constructed, the entire length of chromosome 5 becomes 31 Mb. Although the internal moiety of the centromeric region has not been sequenced yet because of extremely high repetition, the result of sequence analysis from both sides toward the inside strongly suggests that the centromeric region is composed of the central 2.9-Mb domain consisting of mainly 180-bp repeats and Athila retrotransposons and flanking regions containing various types of transposons. On the basis of these observations, a structural model for the centromeric region is discussed.
Poly(A) shortening and degradation of the 3' A+U-rich sequences of human c-myc mRNA in a cell-free system. (1988)

The early steps in the degradation of human c-myc mRNA were investigated, using a previously described cell-free mRNA decay system. The first detectable step was poly(A) shortening, which generated a pool of oligoadenylated mRNA molecules. In contrast, the poly(A) of a stable mRNA, gamma globin, was not excised, even after prolonged incubation. The second step, degradation of oligoadenylated c-myc mRNA, generated decay products whose 3' termini were located within the A+U-rich portion of the 3' untranslated region. These products disappeared soon after they were formed, consistent with rapid degradation of the 3' region. In contrast, the 5' region, corresponding approximately to c-myc exon 1, was stable in vitro. The data indicate a sequential degradation pathway in which 3' region cleavages occur only after most or all of the poly(A) is removed. To account for rapid deadenylation, we suggest that the c-myc poly(A)-poly(A)-binding protein complex is readily dissociated, generating a protein-depleted poly(A) tract that is no longer resistant to nucleases.
Psychedelics Improve the Mental Health of Rats (2019)

Introduction Psilocybin has recently demonstrated profound efficacy to alleviate depression and anxiety in several clinical trials and has received Breakthrough Status by the FDA. Symptomatic relief after only one or two therapeutic treatments last for at least several months in the vast majority of individuals. It is unclear whether the persistent antidepressant and anxiolytic effects are a psychological integration of the subject's personal experience while under the influence of the drug, or are a consequence of neurochemical changes induced by psilocybin that correct abnormalities leading to a healthier brain state. To distinguish between these possibilities, we investigated the antidepressant and anxiolytic effects of psilocybin in a rat model of treatment resistant depression, Wistar‐Kyoto (WKY) rats. Rats do not, as we currently believe, have a sense of self to reflect upon during a psychedelic experience. Therefore, if the effects are purely psychological, psilocybin should not occasion long lasting therapeutic effects as are seen in humans. Objective To evaluate the long‐term effects of psychedelics on depressive‐like and anxiety‐like behaviors in a rat model of depression. Methods Two experiments were performed in which rats were administered a single bolus dose of saline or treatment in saline vehicle: psilocybin (1 mg/kg), lysergic acid diethylamide (LSD, 0.15 mg/kg), or ketamine (5.0 mg/kg) intraperitoneally at a volume of 1 mL/kg. Saline (experiment 1, n =8) and repeat measures psilocybin (experiment 1, n =8) groups were evaluated in the Forced Swim Test (FST) weekly for five weeks, and then the Evaluated Plus Maze (EPM) on the sixth week. Interval psilocybin (experiment 1, n =8), saline (experiment 2, n =6), LSD (experiment 2, n =6), and ketamine (experiment 2, n =6) were evaluated in the FST a single time on the fifth week, and then in the EPM on the sixth week. All measures were evaluated with one‐way ANOVA using Holm‐Sidak post hoc , or with t‐test as appropriate. Results Remarkably, we have found that a single treatment with psilocybin produces context‐dependent, long lasting antidepressant‐like ( p =0.046, p =0.026, and p &lt;0.0001) and anxiolytic effects ( p =0.039) in male WKY rats as measured by the FST and EPM. We have also found that LSD, a related psychedelic, produces a long lasting antidepressant‐like effect in male WKY rats ( p =0.003), while ketamine does not. Conclusions These results indicate that at least a substantial portion of the ability of psychedelics to produce long lasting therapeutic effects has a biological basis and can be studied in animal models. Support or Funding Information This work was supported by Eleusis, PBC. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Folate analogs altered in the C9-N10 bridge region. 14. 11-Oxahomofolic acid, a potential antitumor agent (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFolate analogs altered in the C9-N10 bridge region. 14. 11-Oxahomofolic acid, a potential antitumor agentM. G. Nair, Colleen Saunders, Shiang-Yuan Chen, Roy L. Kisliuk, and Y. GaumontCite this: J. Med. Chem. 1980, 23, 1, 59–65Publication Date (Print):January 1, 1980Publication History Published online1 May 2002Published inissue 1 January 1980https://pubs.acs.org/doi/10.1021/jm00175a011https://doi.org/10.1021/jm00175a011research-articleACS PublicationsRequest reuse permissionsArticle Views132Altmetric-Citations13LEARN 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
Resistance exercise and nutrition to counteract muscle wasting (2009)

Loss of muscle mass is an unfavourable consequence of aging and many chronic diseases. The debilitating effects of muscle loss include declines in physical function and quality of life and increases in morbidity and mortality. Loss of muscle mass is the result of a decrease in muscle protein synthesis, an increase in muscle protein degradation, or a combination of both. Much research on muscle wasting has tended to focus on preventing muscle protein breakdown, and less attention has been paid to providing adequate stimulation to increase muscle protein synthesis. In this review, we present evidence to suggest that interventions aimed at increasing muscle protein synthesis represent the most effective countermeasure for preventing, delaying, or reversing the loss of skeletal muscle mass experienced in various muscle wasting conditions. Based on results from acute and chronic studies in humans in a wide variety of wasting conditions, we propose that resistance exercise training combined with appropriately timed protein (likely leucine-rich) ingestion represents a highly effective means to promote muscle hypertrophy, and may represent a highly effective treatment strategy to counteract the muscle wasting tassociated with aging and chronic disease.
Human Tripartite Motif 5α Domains Responsible for Retrovirus Restriction Activity and Specificity (2005)

The tripartite motif 5alpha protein (TRIM5alpha) is one of several factors expressed by mammalian cells that inhibit retrovirus replication. Human TRIM5alpha (huTRIM5alpha) inhibits infection by N-tropic murine leukemia virus (N-MLV) but is inactive against human immunodeficiency virus type 1 (HIV-1). However, we show that replacement of a small segment in the carboxy-terminal B30.2/SPRY domain of huTRIM5alpha with its rhesus macaque counterpart (rhTRIM5alpha) endows it with the ability to potently inhibit HIV-1 infection. The B30.2/SPRY domain and an additional domain in huTRIM5alpha, comprising the amino-terminal RING and B-box components of the TRIM motif, are required for N-MLV restriction activity, while the intervening coiled-coil domain is necessary and sufficient for huTRIM5alpha multimerization. Truncated huTRIM5alpha proteins that lack either or both the N-terminal RING/B-Box or the C-terminal B30.2/SPRY domain form heteromultimers with full-length huTRIM5alpha and are dominant inhibitors of its N-MLV restricting activity, suggesting that homomultimerization of intact huTRIM5alpha monomers is necessary for N-MLV restriction. However, localization in large cytoplasmic bodies is not required for inhibition of N-MLV by huTRIM5alpha or for inhibition of HIV-1 by chimeric or rhTRIM5alpha.
Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant-Negative EGFR-CD533 Enhances Malignant Glioma Cell Radiosensitivity (2004)

We conclude that EGFRvIII confers significant radioresistance to tumor cells through enhanced cytoprotective responses, and we have demonstrated that dominant-negative EGFR-CD533 effectively inhibits EGFRvIII function. These data affirm the broad potential of EGFR-CD533 to radiosensitize human malignant glioma cells.
p53 Cellular Tumor Antigen: Analysis of mRNA Levels in Normal Adult Tissues, Embryos, and Tumors (1985)

The relative levels of mRNA specific for the mouse p53 cellular tumor antigen were determined in various normal adult tissues, embryos, and tumors. All tumors studied contained concentrations of p53 mRNA well above those present in most normal tissues. Normal spleen, however, had p53 mRNA levels comparable to those found in some tumors, despite the fact that they contained barely detectable p53 protein. This apparent discrepancy was found to be due to the extremely rapid turnover rate of p53 in the spleen (half-life, approximately equal to 6 min). In developing fetuses, a marked reduction of p53 mRNA levels was manifest from day 11 onwards, whereas the levels during organogenesis (days 9 to 11) were comparable to those found in undifferentiated embryonic stem cells and in some tumors.
Formation of Hetero-Boroxines: Dynamic Combinatorial Libraries Generated through Trimerization of Pairs of Arylboronic Acids (2007)

Condensation of pairs of arylboronic acids provided homo-and hetero-boroxines in solution as evidenced from NMR spectra, and those boroxines were detected in the gas phase by GC-MS spectrometry.Equilibrium constants for the formation of these boroxines in solution were obtained through integration of pertinent signals in the NMR spectra of the mixtures of boronic acids.Boroxines, cyclic anhydrides of boronic acids, are six-membered inorganic heterocycles that have been used as flame retardant materials, 1 dopants that enhance lithium ion transfer in polymer electrolytes, 2 nonlinear optical materials, 3 and agents that expand the functional and structural complexity of polymeric materials. 4Two attractive features of boroxines are their C 3 -symmetric tripodal structures 5 and Lewis acidity, 6 which provides the additional possibility of functionalizing the boroxine core though noncovalent interactions.Recently, we 7 and the Kua group 8 reported the thermodynamics of formation of boroxines from boronic acids.The equilibrium constants between the boronic acids and the boroxines in the presence of water have been measured using NMR spectroscopy, and a computational study has provided details of their thermodynamic and kinetic behavior.Those reports, however, discussed only homo-boroxines assembled from single monomeric boronic acids.In this paper, we describe the formation and stabilities of hetero-arylboroxines (Scheme 1).We employed several symmetrical arylboronic acids (1-5) to determine whether it would be easy to analyze their resulting hetero-and homo-boroxines using 1 H NMR spectroscopy (Figure 1).The rates of formation and hydrolysis of the boroxines were slow on the NMR spectroscopic timescale at room temperature, as reported previously. 7The 1 H NMR spectra (CDCl 3 ) of mixtures of pairs of these boronic This Paper id dedicated to Professor Dr. Ekkehard Winterfeldt on the occasion of his 75 th birthday.acids in the presence of water provided evidence for formation of their corresponding two homo-and two hetero-boroxines, respectively.For example, the 1 H NMR spectrum of a mixture of 1 and 2 (Figure 2) displays an array of well-defined signals.B(OH) 2 B(OH) 2 O B O B O B O B O B
A fast optimization algorithm for multicriteria intensity modulated proton therapy planning (2010)

The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.
Thiazole and its derivatives (1979)

Mesoionic Thiazoles (M. Begtrup and C. Roussel). Cyanine Dyes Derived from Thiazolium Salts (H. Larive and R. Dennilaule). Selenazole and Derivatives (R. Guglielmetti). Subject and Author Index.
Treatment of refractory Wegener's granulomatosis with humanized monoclonal antibodies (1996)

Conventional immunosuppression for systemic vasculitides is limited by substantial side-effects, cumulative drug toxicity and refractoriness in some patients. Six Wegener's granulomatosis patients who had been refractory to conventional therapy for at least 6 months, were treated with humanized monoclonal antibodies specific to lymphocyte CD52 or CD4 antigens. Diagnosis was on clinicopathological grounds, supported by the presence of autoantibodies to Proteinase 3. Histological evidence of persistent disease activity was obtained for each patient. Humanized monoclonal anti-CD52, with or without anti-CD4, was given intravenously up to 40 mg/day for up to 10 days. Remission, (programmed withdrawal of drug therapy without return of refractory disease) was achieved in all patients. Cytotoxic drugs were discontinued at the time of monoclonal antibody treatment and not used again; steroids were withdrawn gradually. Four patients relapsed at 1.5, 5, 10 and 18 months, and were treated successfully with further monoclonal antibody therapy alone. Three years after the study began, five patients are well; one patient died at surgery whilst in remission. Humanized monoclonal antilymphocyte antibodies may provide an effective treatment in patients with systemic vasculitis which is refractory to steroids or cytotoxic agents, or who are intolerant of these drugs.
Distinct phenotypes distinguish the molecular classes of Angelman syndrome (2001)

Clinically, we were unable to distinguish between UPD and ID patients, suggesting that 15q11-q13 contains the only significant maternally expressed imprinted genes on chromosome 15.
Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice. (1977)

Nude mice of NIH/Swiss background were utilized for the heterotransplantation of a tissue culture cell line derived from a human prostate adenocarcinoma metastatic to the brain. These cells, which had been grown in vitro for 13 passages, formed solid tumors when injected s.c. into nude mice. The cell line DU 145 has been passaged 60 times in vitro over a period of 18 months. Tumors removed from the mice were serially transplanted to additional mice and reestablished in vitro. Light-microscopic analysis of the tumor grown in nude mice revealed a strong similarity to the patient's metastatic tumor. The ultrastructure of the tumor cells propagated in nude mice was compared to that of the original human tumor cells and to the tissue culture cells, both before and after passage in nude mouse. No major differences were detected. Karyotypic analysis of the tumor cells grown in vitro before mouse passage, grown in nude mouse, and grown in vitro after mouse passage indicated chromosomal identity and consistent marker chromosomes: three large acrocentric chromosomes and metacentric minute chromosomes.
Video Quality Experts Group: current results and future directions (2000)

The Video Quality Experts Group (VQEG) was formed in October 1997 to address video quality issues. The group is composed of experts from various backgrounds and affiliations, including participants from several internationally recognized organizations working int he field of video quality assessment. The first task undertaken by VQEG was to provide a validation of objective video quality measurement methods leading to recommendations in both the telecommunications and radiocommunication sectors of the International Telecommunications Union. To this end, VQEG designed and executed a test program to compare subjective video quality evaluations to the predictions of a number of proposed objective measurement methods for video quality in the bit rate range of 768 kb/s to 50 Mb/s. The results of this test show that there is no objective measurement system that is currently able to replace subjective testing. Depending on the metric used for evaluation, the performance of eight or nine models was found to be statistically equivalent, leading to the conclusion that no single model outperforms the others in all cases. The greatest achievement of this first validation effort is the unique data set assembled to help future development of objective models.
A robust superhydrophobic and superoleophobic surface with inverse-trapezoidal microstructures on a large transparent flexible substrate (2010)

A robust superhydrophobic and superoleophobic surface is demonstrated. On a large-size template of the transparent polydimethylsiloxane (PDMS) elastomer surface, perfectly ordered microstructures with an inverse-trapezoidal cross section are fabricated with two consecutive PDMS replication processes and a three-dimensional diffuser lithography technique. The hydrophobicity and transparency were improved by additional coating of a fluoropolymer layer. The robustness of superhydrophobicity was confirmed by the water droplet impinging test. This transparent, flexible, and superhydrophobic surface provides a new approach for self-cleaning surfaces.
Factor Va Alters the Conformation of the Na+-Binding Loop of Factor Xa in the Prothrombinase Complex (2008)

Structural and mutagenesis data have indicated that the 220-loop of thrombin is stabilized by a salt-bridge between Glu-217 and Lys-224, thereby facilitating the octahedral coordination of Na (+) with contributions from two carbonyl O atoms of Arg-221a and Lys-224. All three residues are also conserved in fXa and the X-ray crystal structure of fXa indicates that both Glu-217 and Lys-224 are within hydrogen-bonding distance from one another. To investigate the role of these three residues in the catalytic function of fXa and their contribution to interaction with Na (+), we substituted them with Ala and characterized their properties in both amidolytic and proteolytic activity assays. The results indicate that the affinity of all three mutants for interaction with Na (+) has been impaired. The mutant with the greatest loss of affinity for Na (+) (E217A or E217Q) also exhibited a dramatic impairment ( approximately 3-4 orders of magnitude) in its activity toward both synthetic and natural substrates. Interestingly, factor Va (fVa) restored most of the catalytic defect with prothrombin, but not with the synthetic substrate. Both Glu-217 mutants exhibited a near normal affinity for fVa in the prothrombinase assay, but a markedly lower affinity for the cofactor in a direct-binding assay. These results suggest that, similar to thrombin, an ionic interaction between Glu-217 and Lys-224 stabilizes the 220-loop of fXa for binding Na (+). They further support the hypothesis that the Na (+) and fVa-binding sites of fXa are energetically linked and that a cofactor function for fVa in the prothrombinase complex involves inducing a conformational change in the 220-loop of fXa that appears to stabilize this loop in the Na (+)-bound active conformation.