gebhart/patrepeval huggingface dataset:
The Rabbit Antibody Repertoire as a Novel Source for the Generation of Therapeutic Human Antibodies (2000)

The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic applications for decades, would be an attractive source for the generation of therapeutic human antibodies. The humanization of rabbit antibodies, however, has not been reported. Here we use phage display technology to select and humanize antibodies from rabbits that were immunized with human A33 antigen which is a target antigen for the immunotherapy of colon cancer. We first selected rabbit antibodies that bind to a cell surface epitope of human A33 antigen with an affinity in the 1 nm range. For rabbit antibody humanization, we then used a selection strategy that combines grafting of the complementarity determining regions with framework fine tuning. The resulting humanized antibodies were found to retain both high specificity and affinity for human A33 antigen.
The animal model of human amnesia: long-term memory impaired and short-term memory intact. (1994)

Normal monkeys and monkeys with lesions of the hippocampal formation and adjacent cortex (the H+ lesion) were trained on the delayed nonmatching to sample (DNMS) task with a delay of 0.5 s between the sample and the choice. The animals with H+ lesions learned the task normally at this short delay and also exhibited the same pattern of response latencies as normal monkeys. This finding contrasts with previous observations that initial learning of the DNMS task with delays of 8-10 s is impaired after H+ lesions. The absence of an impairment at a delay of 0.5 s indicates that the H+ lesion does not affect short-term memory. In contrast, when monkeys with H+ lesions were tested at longer delays (> 30 s), an impairment was observed. This selective impairment occurred when the delays were presented sequentially (from 0.5 s to 10 min) and also when delays were presented in a mixed order (1 s, 1 min, and 10 min). The data indicate that the H+ lesion produces a selective impairment in long-term memory, in the absence of a detectable deficit in short-term memory or perception. Accordingly, the findings confirm the long-standing idea, based primarily on studies of humans, that short-term memory is independent of medial temporal lobe function. The findings thereby establish an important parallel between memory impairment in monkeys and humans and provide additional support for the validity of the animal model of human amnesia in the monkey.
Control of enzyme enantioselectivity by the reaction medium (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTControl of enzyme enantioselectivity by the reaction mediumTakayasu. Sakurai, Alexey L. Margolin, Alan J. Russell, and Alexander M. KlibanovCite this: J. Am. Chem. Soc. 1988, 110, 21, 7236–7237Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/ja00229a061https://doi.org/10.1021/ja00229a061research-articleACS PublicationsRequest reuse permissionsArticle Views388Altmetric-Citations196LEARN 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
Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles (2013)

Lipid nanoparticles (LNPs) encapsulating short interfering RNAs that target hepatic genes are advancing through clinical trials, and early results indicate the excellent gene silencing observed in rodents and nonhuman primates also translates to humans. This success has motivated research to identify ways to further advance this delivery platform. Here, we characterize the polyethylene glycol lipid (PEG-lipid) components, which are required to control the self-assembly process during formation of lipid particles, but can negatively affect delivery to hepatocytes and hepatic gene silencing in vivo. The rate of transfer from LNPs to plasma lipoproteins in vivo is measured for three PEG-lipids with dialkyl chains 14, 16, and 18 carbons long. We show that 1.5 mol % PEG-lipid represents a threshold concentration at which the chain length exerts a minimal effect on hepatic gene silencing but can still modify LNPs pharmacokinetics and biodistribution. Increasing the concentration to 2.5 and 3.5 mol % substantially compromises hepatocyte gene knockdown for PEG-lipids with distearyl (C18) chains but has little impact for shorter dimyristyl (C14) chains. These data are discussed with respect to RNA delivery and the different rates at which the steric barrier disassociates from LNPs in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e139; doi:10.1038/mtna.2013.66; published online 17 December 2013.
Recommendations for the use of natriuretic peptides in acute cardiac care: A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care (2011)

Recommendations for the use of natriuretic peptides in acute cardiac care : A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care
Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds (2011)

The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed.
Human Dendritic Cells Produce TGF-β1 under the Influence of Lung Carcinoma Cells and Prime the Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells (2009)

Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present in the tumor milieu can alter the maturation of DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human DCs increased the expression of TGF-beta1 transcripts following culture with human lung carcinoma cells (LCCs). These DCs produced increased amounts of TGF-beta1 protein compared with DCs not exposed to tumor cells. LCCs also decreased the expression of CD86 and HLA-DR by immature DCs. Furthermore, LCCs decreased CD86 expression and the production of TNF-alpha and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs into cells producing TGF-beta1. These TGF-beta1-producing DCs were poor at eliciting the activation of naive CD4(+) T cells and sustaining their proliferation and differentiation into Th1 (IFN-gamma(+)) effectors. Instead, TGF-beta1-producing DCs demonstrated an increased ability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress the proliferation of T lymphocytes. These results identify a novel mechanism by which the function of human DCs is altered by tumor cells and contributes to the evasion of the immune response.
Lithium-water power source for low power-long duration undersea applications (2002)

Battery requirements for deep-ocean operation in areas of low dissolved oxygen were set at 2 watts (for a minimum of one year) at an operating voltage of at least 0.75 volts. The maximum battery system weight was not to exceed 50 lbs. The ability of the lithium-water electrochemical couple to satisfy these requirements has been demonstrated. Short-term high-pressure testing defined performance up to 10000 psi. Stable multiweek performance was demonstrated at ambient pressure. Specific energy based on lithium ranged from 1800 to 2400 Wh/kg, sufficiently high to achieve the system weight goal of 50 lbs. A proprietary electrolyte management scheme was developed to admit the proper flow of water into the battery while retaining the electrolyte alkalinity required to control the reactivity of the lithium. The scheme was demonstrated over a six month test period. The lithium-water electrochemistry, integrated system concept, test results, and the design configurations chosen for ocean deployment are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Multiphoton fabrication of chemically responsive protein hydrogels for microactuation (2008)

We report a method for creating stimuli-responsive biomaterials in which scanning nonlinear excitation is used to photocrosslink proteins at submicrometer 3D coordinates. Proteins with differing hydration properties can be combined to achieve tunable volume changes that are rapid and reversible in response to changes in chemical environment. Protein matrices having arbitrary 3D topographies and definable density gradients over micrometer dimensions provide the ability to effect rapid (<1 sec) and precise mechanical manipulations by means of changes in hydrogel size and shape, and applicability of these materials to cell biology is shown through the fabrication of responsive bacterial cages.
The Hemodynamics of Human Septic Shock Relate to Circulating Innate Immunity Factors (2010)

The role of innate immunity, e.g., complement activation and cytokine release in the hemodynamic alterations in the course of human septic shock is largely unknown. We prospectively studied 14 consecutive septic shock patients with a pulmonary artery catheter in place. For 3 days after admission, hemodynamic variables and plasma levels of C3a, a product of complement activation, and interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) were measured 6-hourly. Doses of vasoactive drugs were recorded. Of the 14 patients, 8 died in the ICU. Patients had a hyperdynamic circulation with tachycardia, mild hypotension, increased cardiac index, peripheral vasodilation and myocardial depression. C3a, IL-6 and TNF-α plasma levels were supranormal in 123 of 138 (89%), 132 of 138 (96%) and 83 of 111 (75%) measurements, respectively. Independently of blood culture results, treatment with vasoactive drugs and outcome, mean arterial blood pressure and systemic vascular resistance index were lower when IL-6 levels were higher and left ventricular function was less depressed when C3a levels were higher in the course of septic shock. The TNF-α levels did not invariably relate to peripheral vascular and myocardial function parameters. Our serial observations suggest that, in human septic shock, peripheral vasodilation is most strongly and independently, of all inflammatory factors, associated with IL-6 release, whereas complement activation partly offsets the myocardial depression of the syndrome. Innate immunity factors may thus differ in their contribution to the course of hemodynamic abnormalities of septic shock.
1994 Consensus Conference on Acute GVHD Grading. (1995)

Grading acute graft-versus-host disease (GVHD) is usually based on quantification of rash, serum bilirubin and diarrhea. Standard criteria have been developed and used for > 20 years by most transplant centers. However, neither the standard GVHD grading system nor any of several revisions has been validated in the context of GVHD prophylaxis with cyclosporine. The 1994 Consensus Conference on Acute GVHD Grading held in Keystone in January 1994 provided an opportunity to: (1) review data regarding these standard criteria; (2) determine if there are sufficient data to revise these criteria; and (3) develop recommendations for reporting results of GVHD prevention trials. Data were provided for 8249 patients from 12 large transplant centers and 2 transplant registries. Standard GVHD grading criteria were found to distinguish different mortality risks and treatment response rates. Analysis of new data suggested that persistent nausea with histologic evidence of GVHD but no diarrhea be included as stage 1 gastrointestinal GVHD. Additional studies were recommended to evaluate heterogeneity of outcome within GVHD grades prior to making further revisions. To improve comparability between publications, reports of GVHD prevention trials should include an accurate description of the grading system used and should report actuarial rates of grades II-IV and III-IV GVHD corrected for graft failure and potential interventions for early relapse. Additional information should include indications for therapy of GVHD and response.
Early Release of HMGB-1 from Neurons after the Onset of Brain Ischemia (2007)

The nuclear protein high-mobility group box 1 (HMGB-1) promotes inflammation in sepsis, but little is known about its role in brain ischemia-induced inflammation. We report that HMGB-1 and its receptors, receptor for advanced glycation end products (RAGE), Toll-like receptor 2 (TLR2), and TLR4, were expressed in normal brain and in cultured neurons, endothelia, and glial cells. During middle cerebral artery occlusion (MCAO), in mice, HMGB-1 immunostaining rapidly disappeared from all cells within the striatal ischemic core from 1 h after onset of occlusion. High-mobility group box 1 translocation from nucleus to cytoplasm was observed within the cortical periinfarct regions 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 predominantly translocated to the cytoplasm or disappeared in cells that colabeled with the neuronal marker NeuN. Furthermore, RAGE was robustly expressed in the periinfarct region after MCAO. Cellular release of HMGB-1 was detected by immunoblotting of cerebrospinal fluid as early as 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 released from neurons, in vitro, after glutamate excitotoxicity, maintained biologic activity and induced glial expression of tumor necrosis factor alpha (TNFalpha). Anti-HMGB-1 antibody suppressed TNFalpha upregulation in astrocytes exposed to conditioned media from glutamate-treated neurons. Moreover, TNFalpha and the cytokine intercellular adhesion molecule-1 increased in cultured glia and endothelial cells, respectively, after adding recombinant HMGB-1. In conclusion, HMGB-1 is released early after ischemic injury from neurons and may contribute to the initial stages of the inflammatory response.
Absolute Quantification of Proteins Using Standard Peptides and Multiple Reaction Monitoring (2012)

Mass spectrometry (MS) is a powerful tool for protein identification and has therefore become indispensable for proteome studies. In recent years, simple protein identification by MS has become routine, and more attention has been devoted to the MS-based investigation of posttranslational modifications and the quantification of proteins and peptides. Numerous methods and techniques for relative quantification of proteins by MS have emerged and have been applied successfully to answer various questions of protein abundance. Absolute quantification is often applied in clinical research and biomarker discovery, but has also been used to determine protein stoichiometries in protein complexes. However, the number of methods available for absolute quantification is still restricted and often requires the generation of standard peptides containing amino acids labeled with stable isotopes, although label-free approaches are also gaining importance. Complete hydrolysis of the proteins to be quantified is known to be one of the prerequisites for reliable absolute quantification, and selection and suitability of the standard peptides are critical factors in the planning of a quantitative study. Along the different methods to read out quantitative signals by MS, multiple reaction monitoring (MRM) has proven to be most suitable, with a wide linear range. However, analysis by MRM is a targeted approach and each case requires the individual design of suitable assays, which is a time-consuming step during the preliminary analysis. In this chapter, we present various protocols for in-solution hydrolysis, manual selection of suitable standard peptides, and design of MRM transitions.
Chemical and physico-chemical characterization of lignins obtained from ethanol-water fractionation of bagasse (2011)

Organosolv lignins can replace petroleum chemicals such as phenol either partially or totally in various applications. Eight lignins, seven of which corresponded to the ethanol-water fractionation of bagasse and the other to a reference lignin (Alcell®) were analyzed with the aim to evaluate their chemical and physicochemical characteristics. The purity of the lignin fractions was determined by high pressure liquid chromatography (HPLC) and by ash content. Fourier Transform-Infrared Spectroscopy (FTIR) techniques and differential UV spectroscopy were applied to identify the chemical groups in the lignin samples. The molecular weight distribution was determined by size exclusion chromatography (HPSEC). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques were used to determine the mass loss due to the high temperature treatment. The lignins studied showed the presence of p-hydroxyphenyl (H unit) and a greater proportion of guaiacyl (G unit) moieties, lower purity, similar or greater amount of phenolic hydroxyl groups, and higher degradation temperatures, than the Alcell® lignin.
Replication-Defective Vector Based on a Chimpanzee Adenovirus (2001)

An adenovirus previously isolated from a mesenteric lymph node from a chimpanzee was fully sequenced and found to be similar in overall structure to human adenoviruses. The genome of this virus, called C68, is 36,521 bp in length and is most similar to subgroup E of human adenovirus, with 90% identity in most adenovirus type 4 open reading frames that have been sequenced. Substantial differences in the hexon hypervariable regions were noted between C68 and other known adenoviruses, including adenovirus type 4. Neutralizing antibodies to C68 were highly prevalent in sera from a population of chimpanzees, while sera from humans and rhesus monkeys failed to neutralize C68. Furthermore, infection with C68 was not neutralized from sera of mice immunized with human adenovirus serotypes 2, 4, 5, 7, and 12. A replication-defective version of C68 was created by replacing the E1a and E1b genes with a minigene cassette; this vector was efficiently transcomplemented by the E1 region of human adenovirus type 5. C68 vector transduced a number of human and murine cell lines. This nonhuman adenoviral vector is sufficiently similar to human serotypes to allow growth in 293 cells and transduction of cells expressing the coxsackievirus and adenovirus receptor. As it is dissimilar in regions such as the hexon hypervariable domains, C68 vector avoids significant cross-neutralization by sera directed against human serotypes.
Role of Glutamine-151 of Human Immunodeficiency Virus Type-1 Reverse Transcriptase in RNA-Directed DNA Synthesis (1997)

Glutamine-151 of HIV-1 RT has been shown to be a catalytically important residue through the characterization of its mutant phenotype Glu151Ala (Sarafianos et al., 1995a). To further understand the role of this residue, we have extended this analysis to include polymerization on natural RNA template in addition to DNA template. We find that Q151A mutant exhibited a severe reduction in the polymerase activity without any significant effect on the affinity for dNTP substrate. Unlike DNA-directed reactions, the rate-limiting step for RNA-directed reactions does not appear to be either at the dNTP binding step or the chemical step. Analysis of the products formed on natural heteromeric HIV-genomic RNA template annealed with an 18-mer DNA primer with a sequence complementary to the primer binding site (PBS) has shown that addition of nucleotides is nonlinear with time since the enzyme appears to stall on the RNA template following the incorporation of the first nucleotide. The Q151A mutant was found to be nearly devoid of pyrophosphorolytic activity on a RNA-PBS template-primer. Similar properties have been previously reported for a mutant of R72 (R72A) of HIV-1 RT (Sarafianos et al., 1995b). However, R72 was implicated in stabilizing the transition state ternary complex before and after the phosphodiester bond formation (Kaushik et al., 1996; Sarafianos et al., 1995b). Our results with Q151A suggest that the side chain of Q151 may help stabilize the side chain of R72, and the loss of pyrophosphorolysis activity observed with the Q151 mutant may be the indirect manifestation of this stabilizing effect on R72. These observations point to the functional interdependence of residues Q151 and R72 in the polymerase function of the enzyme. An analysis of the 3D model structure of HIV-1 RT bound to DNA-DNA and RNA-DNA template-primer reveals that the guanidine hydrogen of R72 seems to stabilize Q151 by hydrogen bonding with its amide oxygen. A systematic conformational search of the side chain of Q151 also suggests a stable orientation where its specific interaction with the base of the RNA template may aid in stabilizing it.
Synthesis and Pairing Properties of α‐Tricyclo‐DNA (2006)

We describe the synthesis of the phosphoramidite building blocks of alpha-tricyclo-DNA (alpha-tc-DNA) covering all four natural bases, starting from the already known corresponding alpha-tc-nucleosides. These building blocks were used for the preparation of three alpha-tc-oligonucleotide 10-mers representing a homopurine, a homopyrimidine, and a mixed purine/pyrimidine base sequence. The base-pairing properties with complementary parallel and antiparallel oriented DNA and RNA were studied by UV-melting analysis and CD spectroscopy. We found that alpha-tc-DNA binds preferentially to parallel nucleic acid complements through Watson-Crick duplex formation, with a preference for RNA over DNA. In comparison with natural DNA, alpha-tc-DNA shows equal to enhanced affinity to RNA and also pairs to antiparallel DNA or RNA complements, although with much lower affinity. In the mixed-base sequence these antiparallel duplexes are of the reversed Watson-Crick type, while in the homopurine/homopyrimidine sequences Hoogsteen and/or reversed Hoogsteen pairing is observed. Antiparallel duplex formation of two alpha-tc-oligonucleotides was also observed, although the thermal stability of this duplex was surprisingly low. The base-pairing properties of alpha-tc-DNA are discussed in the context of alpha-DNA, alpha-RNA, and alpha-LNA.