gebhart/patrepeval huggingface dataset:
HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells (2012)

Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB8 overexpression increased the percentage of side population (SP) cells representing CSCs in RCC cells, enhancing their tumor-initiating ability. Conversely, attenuation of DNAJB8 decreased SP cells and reduced tumor-initiating ability. The utility of DNAJB8 as an immunologic target was established in DNA vaccination experiments. Compared with immunization with the tumor-associated antigen survivin, which was expressed in both CSCs and non-CSCs in RCC, immunization with Dnajb8 expression plasmids yielded stronger antitumor effects. Together, our findings suggest that DNAJB8 plays a role in CSC maintenance and that it offers a candidate for CSC-targeting immunotherapy in RCC.
Chirospecific Synthesis of Spirocyclic β-Lactams and Their Characterization as Potent Type II β-Turn Inducing Peptide Mimetics (2005)

[reaction: see text] Starting from natural proline, a practical chirospecific synthesis of spirocyclic beta-lactams of type 2 is described when a methylene moiety showing minimal steric demand is employed as a constraint element for adjusting the dihedral angle psi(i + 1). Employing the concept of self-reproduction of chirality, C-formylation of the oxazolidinone 5 afforded the key intermediate 7 taking advantage of an intermediate protection of the bridging element as a vinyl moiety. NMR- and IR-based conformational studies clearly indicated that spiro-beta-lactams of type 2 can serve as efficient beta-turn nucleators.
Th40 cells (CD4+CD40+ Tcells) drive a more severe form of Experimental Autoimmune Encephalomyelitis than conventional CD4 T cells (2017)

CD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells. Adoptively transferred Th40 cells are present in lesions in the CNS and are associated with wide spread demyelination. Primary Th40 cells from EAE-induced donors adoptively transfer EAE without further in-vitro expansion and without requiring the administration of the EAE induction regimen to the recipient animals. This has not been accomplished with primary, non-TCR-transgenic donor cells previously. If co-injection of Th40 donor cells with Freund's adjuvant (CFA) in the recipient animals is done, the disease course is more severe. The CFA component of the EAE induction regimen causes generalized inflammation, promoting expansion of Th40 cells and infiltration of the CNS, while MOG-antigen shapes the antigen-specific TCR repertoire. Those events are both necessary to precipitate disease. In MS, viral infections or trauma may induce generalized inflammation in susceptible individuals with subsequent disease onset. It will be important to further understand the events leading up to disease onset and to elucidate the contributions of the Th40 T cell subset. Also, evaluating Th40 levels as predictors of disease onset would be highly useful because if either the generalized inflammation event or the TCR-honing can be interrupted, disease onset may be prevented.
Immune Responses of Mice and Human Breast Cancer Patients following Immunization with Synthetic Sialyl‐Tn Conjugated to KLH Plus Detox Adjuvant (1993)

We generated a synthetic epitope, NANA alpha(2-6) GalNAc alpha-O-Crotyl (STn-crotyl), designed to "mimic" the natural O-linked epitope expressed on human carcinoma cells, NANA alpha(2-6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm, and a "vaccine" containing STn-KLH plus DETOX adjuvant was formulated. The immunogenicity of the vaccine was evaluated preclinically in CAF1 mice and subsequently in patients with metastatic breast cancer. The specificity and titers of IgG antibodies were evaluated by kinetic ELISA on synthetic STn-HSA and on ovine submaxillary mucin (OSM) solid phases. Ovine submaxillary mucin is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 micrograms of STn-KLH produced IgG titers ranging from 1:10(4) to 1:10(5) when tested on solid phase OSM. Anti-OSM IgG, both polyclonal and monoclonal antibodies, generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. These monoclonal antibodies also bound to STn determinants on human tumor cell surfaces. Breast cancer patients immunized with 100 micrograms of the same vaccine produced median peak IgG titers 1:1280 measured on STn-HSA and 1:160 on OSM. Hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little evidence that the artificial linker arm (crotyl linker) contributed substantially to either the titer or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha(2-->6)-GalNAc. Small but not large doses of STn-KLH immunogen induced anti-STn DTH responses in mice that were inversely proportional to the antibody responses. Evidence of a clinical response was noted in some of the immunized breast cancer patients, with other patients showing prolonged disease stability.
Out-of-plane spiral-coil inductor self-assembled by locally controlled bimorph actuation (2011)

A method to manufacture 3D microcoils based on locally controlled bimorph actuation is reported. A simple and batch-compatible method for producing out-of-plane spiral structures is developed to create inductors whose inductances are tuned independently of their base dimensions. A 500-nm-thick Cr layer used as the stress layer is patterned on a planar Cu coil to induce plastic deformation of the coil in the vertical direction uniformly, defining the final 3D coil shape. The Cr pattern, as well as the temperature of post-fabrication annealing, is varied to achieve different levels of vertical deformation and inductance of the coils. A maximum vertical expansion of 721 µm is demonstrated to yield a 12% inductance change. The Q factor of 17 and the self-resonance at ∼1.2 GHz are obtained.
DNA sequencing, automation, and the human genome (1990)

DNA sequencing is one of the key analytical operations of modern molecular biology and a crucial element of biotechnology. The principles of DNA sequencing and details of the technologies of both manual, radioisotope-based and automated, fluorescence-based approaches are described. The goals and rationale of the Human Genome Initiative are discussed along with implications for future sequencing technologies. Finally, a glimpse of emerging DNA sequencing technologies is offered.
Biocompatible and Bioactive Surface Modifications for Prolonged In Vivo Efficacy (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTBiocompatible and Bioactive Surface Modifications for Prolonged In Vivo EfficacySteven R. Meyers and Mark W. Grinstaff*View Author Information Departments of Biomedical Engineering and Chemistry, Boston University, Boston, Massachusetts 02215, United States*E-mail: [email protected]Cite this: Chem. Rev. 2012, 112, 3, 1615–1632Publication Date (Web):October 18, 2011Publication History Received30 March 2011Published online18 October 2011Published inissue 14 March 2012https://pubs.acs.org/doi/10.1021/cr2000916https://doi.org/10.1021/cr2000916review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views5647Altmetric-Citations218LEARN 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 SUBJECTS:Alcohols,Cells,Coating materials,Implants,Peptides and proteins Get e-Alerts
Review: Milstein Award Lecture: Interferons and Cancer: Where from Here? (2005)

Interferons (IFNs) remain the most broadly active cytokines for cancer treatment, yet ones for which the full potential is not reached. IFNs have impacted positively on both quality and quantity of life for hundreds of thousands of cancer patients with chronic leukemia, lymphoma, bladder carcinoma, melanoma, and renal carcinoma. The role of the IFN system in malignant pathogenesis continues to enhance understanding of how the IFN system may be modulated for therapeutic advantage. Reaching the full potential of IFNs as therapeutics for cancer will also result from additional understanding of the genes underlying apoptosis induction, angiogenesis inhibition, and influence on immunologic function. Food and Drug Administration (FDA) approval of IFNs occurred less than 20 years ago; after 40 years, third-generation products of early cytotoxics, such as 5- fluorouracil (5FU), are beginning to reach clinical approval. Thus, substantial potential exists for additional application of IFNs and IFN inducers as anticancer therapeutics, particularly when one considers that their pleiotropic cellular and molecular effects have yet to be fully defined.
The saturable high affinity association of factor X to ADP-stimulated monocytes defines a novel function of the Mac-1 receptor. (1988)

Initiation of the coagulation protease cascade as it assembles on cell surfaces requires limited proteolytic activation of the zymogen factor X. Not previously suspected to be the ligand of an organizing receptor on cell surfaces, we now describe that factor X specifically associates with cells of monocyte lineage and we identify the high affinity receptor for this zymogen. Following stimulation with ADP (10 microM), or with the ionophore ionomycin (1 microM), isolated human monocytes bind 125I-factor X in a saturable fashion with a dissociation constant (Kd) of 21.8-44.9 nM. Equilibrium binding analyses indicate that the reaction is optimal at room temperature, requires Ca2+ ions, and saturates at 128,500 +/- 21,300 molecules of 125I-factor X specifically associated with the cell surface. Molar excess of unlabeled factor X inhibits and reverses the binding, whereas the homologous gamma-carboxylated coagulation proteins factors II, VII, IX, IXa, and Xa are without effect. Similarly, chelation of divalent ions immediately dissociates bound 125I-factor X. The monoblast cell line U 937 and the monocytic cell line THP-1 when stimulated with ADP or ionomycin, bind 125I-factor X with characteristics similar to monocytes. Receptor identity was explored using antibodies to the leukocyte adhesive receptors Mac-1, LFA-1, and p150.95. Monoclonal antibodies specific for the alpha subunit of Mac-1 (M 1/70, LM 2/1) or for the common beta subunit (TS 1/18, 60.3) bound equally to resting and ADP- or ionomycin-stimulated cells and also completely blocked the binding of 125I-factor X to stimulated monocytes, U 937, or THP-1 cells. To distinguish between modulatory effects of the monoclonal antibodies and direct spatial hindrance binding of 125I-factor X to Mac-1 was analyzed directly. OKM10 anti-alpha subunit of Mac-1 monoclonal antibody immunoprecipitated 125I-factor X chemically cross-linked to its receptor on stimulated cells. In addition, the complement protein fragment C3bi, which is a recognized ligand for Mac-1, competitively inhibited the association of 125I-factor X. These findings indicate that human blood monocytes and less differentiated cells of this lineage possess an inducible receptor specific for factor X; and also support the conclusion that the heterodimeric leukocyte adhesive receptor Mac-1 functions as the specific receptor structure. We suggest that the novel properties of this receptor may be of importance in the organization and regulation of certain coagulation protease cascades on the monocyte surface.
Peripheral nerve injury from implantation of chronic stimulating electrodes for pain control. (1976)

Complications of implantable stimulating electrodes for pain control are becoming recognized. We present two cases of peripheral nerve injury related to placement of peripheral nerve stimulating electrodes and discuss the relevant literature.
A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens. (1988)

Mitogens evoke many alterations in gene expression in eukaryotic cells. Genes which are activated rapidly and transiently, that are evolutionarily conserved and whose induction is shared by diverse cell types when exposed to different growth stimuli are likely to be of critical importance in transducing mitogenic signals and regulating cellular proliferation. c-myc and c-fos are the only known genes fulfilling these criteria. We report on the molecular cloning of a novel early growth response (egr) gene which also satisfies these conditions. In response to serum, its 3.7 kb mRNA is induced dramatically in mouse fibroblasts reaching a peak level at about 30 minutes that is ten times higher than the maximal value attained by c-fos mRNA. This transcript is induced by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate and is "superinduced" by serum and cycloheximide together. Importantly, the gene is highly induced by different mitogens in a wide array of cell types: insulin stimulated rat hepatoma cells, adenosine diphosphate treated monkey kidney epithelial cells, and phytohemagglutinin stimulated human peripheral blood lymphocytes. Given the many properties that this gene shares with c-myc and c-fos, it may play a key role in the control of cell growth and perhaps in oncogenesis.
Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM Alone and Sequentially With Vaccinia-CEA(6D)-TRICOM, With and Without Granulocyte-Macrophage Colony-Stimulating Factor, in Patients With Carcinoembryonic Antigen–Expressing Carcinomas (2004)

We demonstrated that the CEA-TRICOM vaccines are safe and can generate significant CEA-specific immune responses, and they seem to have clinical benefit in some patients with advanced cancer.
STAT proteins participate in the regulation of the vasoactive intestinal peptide gene by the ciliary neurotrophic factor family of cytokines. (1994)

Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are members of a family of neuropoietic cytokines that have a broad range of actions on many different neuronal populations. In cultured sympathetic neurons, CNTF and LIF induce transcription of the VIP and other neuropeptide genes as part of a program of differentiation. To gain insight into the nuclear events involved in cytokine-mediated activation of the neuropeptide genes involved in neuronal differentiation, we have investigated the mechanisms of transcriptional activation of the vasoactive intestinal peptide (VIP) gene by the CNTF family of cytokines. In the neuroblastoma cell line NBFL, CNTF, LIF, and a related cytokine, oncostatin-M, activate VIP gene transcription through a 180-base pair cytokine response element (CyRE). Deletion analysis of the VIP CyRE showed that multiple regions within the 180 base-pairs are important for cytokine-mediated transcriptional activation of the VIP gene. To one of these regions within the CyRE, cytokine treatment induces binding of a protein complex composed of members of the signal transducers and activators of transcription (STAT) transcription factor family. Mutation of this STAT-binding site attenuates cytokine-mediated transcriptional activation. LIF treatment of primary sympathetic neurons also induced binding of a STAT-containing protein complex to the VIP CyRE. Thus, activation of STAT transcription factors contributes to the induction of the VIp gene by the CNTF family of cytokines and may be involved in cytokine-mediated differentiation of sympathetic neurons.
Identification of factors that contribute to recombinant AAV2 particle aggregation and methods to prevent its occurrence during vector purification and formulation (2005)

Aggregation of recombinant AAV2 results in reduced yield during purification and may have deleterious effects on vector transduction efficiency, biodistribution and immunogenicity following in vivo administration. Studies to elucidate the mechanism of vector aggregation and methods to prevent its occurrence are reported. In excipient screening studies, the sugars sorbitol, sucrose, mannitol, trehalose, or glycerol at concentrations of up to 5% (w/v), or surfactants Tween 80 or Pluronic F68, did not prevent aggregation. Aggregation was prevented by the use of various salts at concentrations corresponding to solution ionic strengths of >200 mM. AAV2 vectors purified by double cesium chloride gradient centrifugation, cation-exchange chromatography, or combined chromatography and gradient centrifugation each demonstrated a similar requirement for ionic strength to prevent aggregation. AAV2 vectors concentrated to 6.7 x 10(13) vector genome (vg)/mL in neutral-buffered isotonic saline resulted in 59+/-6.0% recovery of nonaggregated material compared to 96+/-4.4% recovery in an isotonic formulation with elevated ionic strength. The latter showed no aggregation following storage or after 10 freeze-thaw cycles at -20 degrees C. AAV2 vectors stored for an extended period in an elevated ionic strength formulation retained a high infectivity titer (13 vg/infectious unit) and transduction efficiency. Nuclease digestion of purified AAV2 vectors reduced aggregation, implicating trace amounts of vector surface nucleic acids in interparticle binding.
Monitoring the quality of fluidization using the short‐term predictability of pressure fluctuations (1998)

Abstract In various industrial applications of bubbling fluidized beds, defluidizing parts of the bed or even of the complete bed can occur as a result of agglomeration and sintering of particles due to unintentional maloperation of the bed, changes in operating conditions, or variations in gas or solids feed. Defluidization may be prevented by increasing the gas velocity or changing the solids feed, if the change in the “quality” of the fluidized state of particles is detected early enough. An analysis method is proposed that uses the short‐term predictability of time series of (local) pressure fluctuations in the fluidized bed to detect changes early in the hydrodynamic state of the bed. It is based on the comparison of an original time series of pressure fluctuations with successive time series measured during operation of a fluidized bed. The comparison is based on a discriminating statistic computed for the original time series as well as for each successive series. The null hypothesis that the original and successive time series are similar is rejected if the discriminating statistics of both time series significantly differ. Experimental application of the method is illustrated for fluidization at elevated temperatures (ca. 120°C) of agglomerating plastic particles in a 5‐cm‐ID laboratory fluidized bed. The method recognizes the change in the hydrodynamics due to the incipient agglomeration of the particles. In this particular case the time period between the moment of detection of a significant change in the hydrodynamics and the end of the experiment when the bed becomes defluidized seems sufficiently large to take preventive measures. The average bed‐pressure drop is not a sensitive quantity to detect changes early in the fluidization behavior.
The cytokine factsbook (2001)

Preface. Abbreviations. Section I: The Introductory Chapters Introduction. Organization of the Data. The Cytokine Network. Cytokine Receptor Superfamilies. Section II: The Cytokines and Their Receptors Interleukins. Other Cytokines and Chemokines. Appendix I: Cytokine Standards Appendix II: WWW Sites for DNA and Protein Databases. Appendix III: Internet Resources for Transgenic and Targeted Mutation Research. Index.
Deep learning for computational biology (2016)

Technological advances in genomics and imaging have led to an explosion of molecular and cellular profiling data from large numbers of samples. This rapid increase in biological data dimension and acquisition rate is challenging conventional analysis strategies. Modern machine learning methods, such as deep learning, promise to leverage very large data sets for finding hidden structure within them, and for making accurate predictions. In this review, we discuss applications of this new breed of analysis approaches in regulatory genomics and cellular imaging. We provide background of what deep learning is, and the settings in which it can be successfully applied to derive biological insights. In addition to presenting specific applications and providing tips for practical use, we also highlight possible pitfalls and limitations to guide computational biologists when and how to make the most use of this new technology.
FOUR COLOR FRET DYE NUCLEOTIDE TERMINATORS FOR DNA SEQUENCING (2001)

The synthesis of four color set of energy transfer-dye terminators (8a-8d) starting from p-iodo-beta-phenylalanine was accomplished and their utility in the sequencing reactions has been evaluated.
Tunable nonlinear current–voltage characteristics of three-terminal ballistic nanojunctions (2003)

The current–voltage (I–V) characteristics of three-terminal ballistic junctions (TBJs) fabricated from high-electron-mobility GaInAs/InP quantum-well structures are measured in the six-terminal configuration. These characteristics show strong nonlinear, diode-like behavior, in agreement with recent theoretical calculations. Furthermore, the I–V characteristics are tunable by the voltage applied directly to one branch of the TBJs acting as a gate. An additional tuning of the characteristics of the TBJ devices can be performed using an in-plane side gate. All the presented characteristics are measured at room temperature, which makes TBJ devices promising for future nanoelectronic applications.