gebhart/patrepeval huggingface dataset:
Humanization of murine monoclonal antibodies through variable domain resurfacing. (1994)

Two murine monoclonal antibodies, N901 (anti-CD56) and anti-B4 (anti-CD19), were humanized by a process we call "resurfacing." A systematic analysis of known antibody structures has been used to determine the relative solvent accessibility distributions of amino acid residues in murine and human antibody variable (Fv) regions and has shown that the sequence alignment positions of surface amino acids for human and murine variable region heavy (VH) and light (VL) chains are conserved with 98% fidelity across species. While the amino acid usage at these surface positions creates surface residue patterns that are conserved within species, there are no identical patterns across species. However, surprisingly few amino acid changes need to be made to convert a murine Fv surface pattern to that characteristic of a human surface. Resurfacing was used to change the patterns of surface accessible residues in the Fv regions of the N901 and anti-B4 antibodies to resemble those found on the Fv regions of human antibody sequences. Two different procedures for selecting a human sequence were compared. For anti-B4, a data base of clonally derived human VL-VH sequence pairs was used, while for N901, sequences for VL and VH were independently selected from the Kabat et al. data base [Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. & Gottesman, K. S. (1991) Sequences of Proteins of Immunological Interest (DHHS, Washington, DC), 5th Ed.]. Resurfaced N901 and anti-B4 antibodies had apparent affinities for their cell surface ligands that were identical to those of their respective parent murine antibodies. These data provide evidence that, despite the differences in the surfaces of mouse and human Fv regions, it is possible to substitute one for the other while retaining full antigen binding affinity.
Role of quadratic and cubic spectral phases in ladder climbing with ultrashort pulses (2004)

Two-photon excitation of a quantum ladder system by an ultrashort chirped pulse leads to interferences in the excited-state population, between direct and sequential paths. Experimental results have been obtained in atomic sodium vapor. The presence of several intermediate and final states leads to new phenomena. The interplay between the two sequential paths leads to strongly contrasted oscillations and a large enhancement of the transition probability for precise values of the chirp. A cubic spectral phase modifies significantly the behavior of the quantum interferences and can be used to enhance the two-photon absorption rate.
COBRA: an 1.2 million transistor expandable column FFT chip (2002)

This paper presents an optimized column FFT architecture which utilizes bit-serial arithmetic and dynamic reconfiguration to achieve a complete overlap between computation and communication. As a result, the system can compute a 24-bit precision 1 K point complex FFT transform within 9.25 /spl mu/s, far surpassing the performance of any existing FFT systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Regulation of Feeding and Metabolic Rate and the Prevention of Murine Cancer Cachexia with a Small-Molecule Melanocortin-4 Receptor Antagonist (2005)

Cachexia is metabolic disorder characterized by anorexia, an increased metabolic rate, and loss of lean body mass. It is a relatively common disorder, and is a pathological feature of diseases such as cancer, HIV infection, and renal failure. Recent studies have demonstrated that cachexia brought about by a variety of illnesses can be attenuated or reversed by blocking activation of the melanocortin 4 subtype receptor (MC4-R) within the central nervous system. Although the potential use of central MC4-R antagonists for the treatment of cachexia was supported by these studies, utility was limited by the need to deliver these agents intracerebroventricularly. In the current study, we present a series of experiments demonstrating that peripheral administration of a small molecule MC4-R antagonist can effectively stimulate daytime (satiated) food intake as well as decrease basal metabolic rate in normal animals. Furthermore, this compound attenuated cachexia and preserved lean body mass in a murine cancer model. These data clearly demonstrate the potential of small molecule MC4-R antagonists in the treatment of cachexia and underscore the importance of melanocortin signaling in the development of this metabolic disorder.
Hepatitis Delta: Immunopathogenesis and Clinical Challenges (2010)

Hepatitis delta is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of viral hepatitis in humans. Hepatitis delta occurs only in hepatitis B virus (HBV) surface antigen (HBsAg)-positive individuals as HDV is a defective RNA virus which requires the HBsAg for complete replication and transmission. Eight different HDV genotypes have been described with specific geographic distributions and distinct clinical courses. HDV/HBV co-infection can be associated with complex and dynamic viral dominance patterns. While HDV is frequently the dominating virus not only in HBV/HDV co-infection, but also in HBV/HCV/HDV triple-infected patients, the fluctuating courses of HDV and HBV viremia can be observed in other patients. Chronic HDV infection leads to more severe liver disease than HBV monoinfection with accelerated fibrosis progression, earlier hepatic decompensation and an increased risk for the development of hepatocellular carcinoma. However and in contrast to HCV infection, hepatic decompensation, rather than development of liver cancer, is the first clinical endpoint that develops during the course of infection. So far, only interferon-alpha treatment has proven antiviral activity against HDV in humans and has been linked to improved long-term outcome. Recent studies on the use of pegylated interferon showed a sustained virological response concerning HDV-RNA in about one quarter of the patients. HDV-specific immune responses might be associated with the response to treatment. Novel alternative treatment options, including prenylation inhibitors, are still awaiting clinical development for delta hepatitis. So far, only few studies have investigated immune responses against HDV and HBV in humans.
G-rich Oligonucleotide Inhibits the Binding of a Nuclear Protein to the Ki-ras Promoter and Strongly Reduces Cell Growth in Human Carcinoma Pancreatic Cells (2004)

Oligonucleotides are able to recognize both nucleic acids and proteins with a high degree of specificity and are therefore investigated as a new and innovative class of therapeutic anticancer drugs. In the present study, we have constructed from Panc-1 cells a stable transfectant (AG transfectant) generating constitutively a short transcript (T-22AG), which is potentially capable of forming a triplex with a critical polypurine/polypyrimidine (pur/pyr) motif located in the Ki-ras promoter. Because of the presence of a G-rich element in its sequence, transcript T-22AG was also capable, under physiological conditions, of adopting a tetraplex conformation. We found that the levels of Ki-ras mRNA and p21(RAS) protein in the AG transfectant were, respectively, 52 +/- 8 and 40 +/- 4% of those observed in the control cell lines: untransfected Panc-1 cells and stably transfected Panc-1 cells producing a control transcript (T-22SCR). The downregulation of Ki-ras resulted in a strong reduction of colony formation (42 +/- 7% of the control) and cell proliferation (34 +/- 5% of the control) capacity. As in vitro experiments showed that the G-rich element of T-22AG (22AG) formed with the Ki-ras pur/pyr motif a triplex of low thermodynamic stability, it is unlikely that the strong bioactivity exhibited by transcript T-22AG is mediated by a triplex-based mechanism, although we cannot totally exclude that in vivo polyamine levels may increase the triplex stability. We found that 22AG adopted a tetraplex conformation and competitively inhibited the binding of a nuclear factor to the Ki-ras pur/pyr sequence. This effect was specific and virtually entirely abrogated when 22AG was denatured by heating. Our data showed that transcript T-22AG acted as a molecular aptamer, binding specifically to a nuclear factor essential for Ki-ras expression. The biological implications of this study are discussed.
The RAD6 protein of Saccharomyces cerevisiae polyubiquitinates histones, and its acidic domain mediates this activity. (1988)

The RAD6 gene of the yeast Saccharomyces cerevisiae is required for post-replication repair of UV-damaged DNA, DNA damage-induced mutagenesis, and sporulation. Here we demonstrate that the protein encoded by the RAD6 gene, previously shown to be a ubiquitin-conjugating (E2) enzyme, multiply ubiquitinates histones H2A and H2B efficiently to give products containing as many as seven or more molecules of ubiquitin. We also show that the highly acidic 23-residue RAD6 carboxy-terminal tail domain, which contains a total of 20 acidic residues, is essential for the histone-polyubiquitinating activity. Because the RAD6 polyacidic tail is required for the sporulation function but not for the DNA repair and induced mutagenesis functions of RAD6, the present observations suggest that the histone-polyubiquitinating activity of RAD6 protein is essential for sporulation but not for DNA repair and induced mutagenesis. Attachment of multiple molecules of ubiquitin to histones by RAD6 protein may serve to target the histones for degradation via the ubiquitin-dependent proteolytic system or to alter chromatin structure. The in vitro system for synthesizing polyubiquitinated histones described herein provides a means for investigating these possibilities.
Stereochemistry of microbiological hydroxylation. III. Hydroxylation of 3-benzoyl-3-azabicyclo[3.3.1]nonane with Rhizopus arrhizus. Novel chromic acid oxidations of substrate and product (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereochemistry of microbiological hydroxylation. III. Hydroxylation of 3-benzoyl-3-azabicyclo[3.3.1]nonane with Rhizopus arrhizus. Novel chromic acid oxidations of substrate and productRoy Allen Johnson, Herbert Charles Murray, and Lester M. ReinekeCite this: J. Org. Chem. 1969, 34, 12, 3834–3837Publication Date (Print):December 1, 1969Publication History Published online1 May 2002Published inissue 1 December 1969https://pubs.acs.org/doi/10.1021/jo01264a021https://doi.org/10.1021/jo01264a021research-articleACS PublicationsRequest reuse permissionsArticle Views101Altmetric-Citations8LEARN 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
Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis (2000)

Morphologic polarity is necessary for chemotaxis of mammalian cells. As a probe of intracellular signals responsible for this asymmetry, the pleckstrin homology domain of the AKT protein kinase (or protein kinase B), tagged with the green fluorescent protein (PHAKT-GFP), was expressed in neutrophils. Upon exposure of cells to chemoattractant, PHAKT-GFP is recruited selectively to membrane at the cell's leading edge, indicating an internal signaling gradient that is much steeper than that of the chemoattractant. Translocation of PHAKT-GFP is inhibited by toxin-B from Clostridium difficile, indicating that it requires activity of one or more Rho guanosine triphosphatases.
Design, Modelling and Control of IRST Capacitive MEMS Microphone (2009)

Condenser MEMS microphones are becoming a promising technology to substitute the current standard microphones, and modelling such systems has become very important for designing a condenser microphone fulfilling the given constrains. In this dissertation a deep analysis of&#13;\ncapacitive MEMS microphone has been presented coming up with a complete model which is able to fit the experimental data of the microphone sensitivity. Furthermore, a simple noise model, able to fit the experimental data, has been developed considering the well-know Brownian noise and the more subtle 1/f component, usually neglected. With such models, it is possible to have a reliable estimation of the microphone SNR.&#13;\nMany characterizations have been performed on the produced samples and different problems of the manufacturing process have been highlighted, gaining a deeper understanding on the&#13;\nstructure of the microphone and on the production process.&#13;\nFinally, to reply to the more and more demanding constraints, two applications of control law have been applied: a force feedback and a controller to tune the resonant frequency of the microphone.&#13;\nThis last application shows how a controller can make the system more flexible and reduce the problem of some defects on the production.&#13;\nThe force feedback is a technique already used in MEMS systems, such as gyroscopes and accelerometers, where it has shown to be able to improve the performance of the systems.&#13;\nIn the presented configuration, a force feedback has been implemented in a digital readout interface, realizing the so-called electromechanical sigma delta converter. Its stability has been evaluated and the improvements have been verified experimentally: due to the extra filtering&#13;\naction of the embedded MEMS system inside the converter loop, the A-weighted in-band noise has been reduced from -63dBA to -73dBA.
Blood-based proteomics for personalized medicine: examples from neurodegenerative disease (2008)

http://dx.doi.org/10.1586/14789450.5.1.1
Heterocyclen aus CH‐aciden Nitrilen, VIII. 2‐Amino‐thiophene aus methylenaktiven Nitrilen, Carbonylverbindungen und Schwefel (1966)

Abstract Aliphatische Ketone, Aldehyde sowie β‐Dicarbonylverbindungen reagieren mit methylenaktiven Nitrilen und Schwefel in Gegenwart von Aminen bei Raumtemperatur zu 2‐Aminothiophenen. — Eine Variante der Synthese, die Einwirkung von Schwefel auf vinyloge methylenaktive Nitrile, gestattet auch die Einbeziehung von Alkylarylketonen in die Reaktion.
Adenovirus-mediated transfer of the muscle glycogen phosphorylase gene into hepatocytes confers altered regulation of glycogen metabolism. (1992)

The muscle isozyme of glycogen phosphorylase is potently activated by the allosteric ligand AMP, whereas the liver isozyme is not. In this study we have investigated the metabolic impact of expression of muscle phosphorylase in liver cells. To this end, we constructed a replication-defective, recombinant adenovirus containing the muscle glycogen phosphorylase cDNA (termed AdCMV-MGP) and used this system to infect hepatocytes in culture. AMP-activatable glycogen phosphorylase activity was increased 46-fold 6 days after infection of primary liver cells with AdCMV-MGP. Despite large increases in phosphorylase activity, glycogen levels were only slightly reduced in AdCMV-MGP-infected liver cells compared to uninfected cells or cells infected with wild-type adenovirus. The lack of correlation of phosphorylase activity and glycogen content suggests that the liver cell environment can inhibit the muscle phosphorylase isozyme. This inhibition can be overcome, however, by addition of carbonyl cyanide m-chlorophenylhydrazone (CCCP), which increases AMP levels by 30-fold and causes a much larger decrease in glycogen levels in AdCMV-MGP-infected cells than in uninfected or wild-type adenovirus-infected controls. CCCP treatment also caused a preferential decrease in glycogen content relative to glucagon treatment in AdCMV-MGP-infected hepatocytes (74% versus 11%, respectively), even though the two drugs caused equal increases in phosphorylase a activity. Introduction of muscle phosphorylase into hepatocytes therefore confers a capacity for glycogenolytic response to effectors that is not provided by the endogenous liver phosphorylase isozyme. The remarkable efficiency of adenovirus-mediated gene transfer into primary hepatocytes and the demonstration of altered regulation of glycogen metabolism as a consequence of expression of a non-cognate phosphorylase isozyme may have implications for gene therapy of glycogen storage diseases.
Microvascular responses to hemodilution with Hb vesicles as red blood cell substitutes: influence of O2affinity (1999)

Phospholipid vesicles encapsulating purified hemoglobin (HbV) were developed to provide O2-carrying capacity to plasma expanders. Microvascular perfusion was determined for HbV with different O2 affinity (P50 = 9, 16, and 30 mmHg) prepared by coencapsulating pyridoxal 5'-phosphate (PLP) at the molar ratios of [PLP]/[Hb] = 0, 0.5, and 3, respectively (cf. hamster blood, P50: 28 mmHg), and suspended in 8 g/dl human serum albumin (HSA). Eighty percent of the red blood cell (RBC) mass of conscious Syrian golden hamsters fitted with dorsal skinfold windows was substituted with either of the HbV-HSA suspensions, washed hamster RBC suspended in HSA (RBC-HSA), and HSA alone. All three HbV-HSA groups and RBC-HSA groups showed stable blood pressure and heart rate, which could not be sustained with HSA alone. Only the HbV (P50 = 9)-HSA group showed an increase in arterial O2 tension (89.8 +/- 14.7 mmHg, baseline 58.4 +/- 4.0 mmHg) because of hyperventilation, and microvascular perfusion was decreased, indicating that facilitated O2 unloading of HbV by decreasing the O2 affinity (increasing P50) with PLP as an allosteric effector is important. Microvascular perfusion and microvascular and interstitial O2 tensions in the HbV (P50 = 16 and 30)-HSA groups were significantly higher than those in the HSA group. The O2 release rate from the HbV was 18-32 s-1 vs. 4.4 s-1 for RBC. Functional capillary density was improved from 17 to 41% on average by decreasing P50 from 30 to 16 mmHg, which appears to be an optimal value for the P50 in this system.
A Strategy for Macrocyclic Ring Closure and Functionalization Aimed toward Split-Pool Syntheses (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Strategy for Macrocyclic Ring Closure and Functionalization Aimed toward Split-Pool SynthesesDaesung Lee, Jason K. Sello, and Stuart L. SchreiberView Author Information Howard Hughes Medical Institute & Institute of Chemistry and Cell Biology (ICCB) Department of Chemistry and Chemical Biology Harvard University, Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1999, 121, 45, 10648–10649Publication Date (Web):October 30, 1999Publication History Received27 July 1999Published online30 October 1999Published inissue 1 November 1999https://pubs.acs.org/doi/10.1021/ja992658mhttps://doi.org/10.1021/ja992658mrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1380Altmetric-Citations88LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Conformation,Macrocycles,Metathesis,Oligomers,Organic compounds Get e-Alerts
Molecular characterization of a t(11;14)(q23;q32) chromosome translocation in a B-cell lymphoma. (1990)

We have analyzed the molecular features of a t(11;14)(q23;q32) chromosome translocation of a cell line established from a B-cell lymphoma. Somatic hybrid cells carrying the 11q- and/or 14q+ chromosome(s) were produced in order to map the breakpoints. Southern blot analyses of DNAs from these hybrid cell lines together with various probes from the IGH locus on chromosome 14 and the ETS-1 and CD3 genes on chromosome 11 showed that the breakpoints of the translocation occurred between the constant regions of the C phi gamma and C gamma 2 genes on chromosome 14 and between the CD3 and ETS-1 genes on chromosome 11. The t(11;14)(q23;q32) translocation does not seem to involve the same mechanism that is responsible for translocations occurring at the immunoglobulin heavy chain joining segment (JH).
Radiometal-Labelled Macrocyclic Chelator-Derivatised Somatostatin Analogue with Superb Tumour-Targeting Properties and Potential for Receptor-Mediated Internal Radiotherapy (1999)

A highly stable octacoordinated Y-DOTA-D-Phe-amide (see picture) allows the first use of the powerful β-emitter 90Y, coupled to a bioactive peptide, in internal radiotherapy of cancer. The same peptide labelled with the γ-emitter, 67Ga, shows improved biodistribution as a consequence of the hexacoordination of the GaIII complex with a pendant, ionised, acetic acid group.
Bcl-2 initiates a new category of oncogenes: regulators of cell death (1992)

PECIFIC CHROMOSOMAL translocations are recur-S rently found in distinct types of ma1ignan~ies.l.~ Indeed, many of these interchromosomal translocations are essentially pathognomonic for a given tumor. The molecular cloning of chromosomal breakpoints has proven a rich source of novel proto-oncogenes. Experimental approaches indicate that deregulation of these genes represents a primary pathogenic event in the generation of tumors. Determining the normal developmental role of each gene promises to deliver insights into their oncogenic mechanism. The lessons provided from the study of one such oncogene, Bcl-2, argue that understanding the functional roles of genes found at breakpoints will have an enormous impact upon mammalian biology. Bcl-2 was discovered at the t( 14; 18)(q32;q21) breakpoint, the cytogenetic hallmark of human follicular l y m p h ~m a . ~-~ Bcl-2 is novel among proto-oncogenes in that it localizes to mitochondria.8 Moreover, Bcl-2 shows the unique functional role of blocking programmed cell death independent of affecting proliferation.