gebhart/patrepeval huggingface dataset:
Heterelogous expression of mutated HLA-G decreases immunogenicity of human embryonic stem cells and their epidermal derivatives (2014)

Human embryonic stem cells (hESCs) are capable of extensive self-renewal and expansion and can differentiate into any somatic tissue, making them useful for regenerative medicine applications. Allogeneic transplantation of hESC-derived tissues from results in immunological rejection absent adjunctive immunosuppression. The goal of our study was to generate a universal pluripotent stem cell source by nucleofecting a mutated human leukocyte antigen G (mHLA-G) gene into hESCs using the PiggyBac transposon. We successfully generated stable mHLA-G(EF1α)-hESC lines using chEF1α promoter system that stably expressed mHLA-G protein during prolonged undifferentiated proliferation andin differentiated embryoid bodies as well as teratomas. Morphology, karyotype, and telomerase activity of mHLA-G expressing hESC were normal. Immunofluorescence staining and flow cytometry analysis revealed persistent expression of pluripotent markers, OCT-3/4 and SSEA-4, in undifferentiated mHLA-G(EF1α)-hESC. Nucleofected hESC formed teratomas and when directed to differentiate into epidermal precursors, expressed high levels of mHLA-G and keratinocyte markers K14 and CD29. Natural killer cell cytotoxicity assays demonstrated a significant decrease in lysis of mHLA-G(EF1a)-hESC targets relative to control cells. Similar results were obtained with mHLA-G(EF1α)-hESC-derived epidermal progenitors (hEEP). One way mixed T lymphocyte reactions unveiled that mHLA-G(EF1a)-hESC and -hEEP restrained the proliferative activity of mixed T lymphocytes. We conclude that heterologous expression of mHLA-G decreases immunogenicity of hESCs and their epidermal differentiated derivatives.
Enriching Mutant Sequences by Modulating the Denaturation Time during PCR (2014)

To the Editor:

For minor and major DNA alleles, coamplification at lower denaturation temperature-PCR (COLD-PCR)1 selectively enriches minority alleles from mixtures of wild-type and mutation-containing sequences without a priori knowledge of the type or position of a mutation within a sequence (1). Since its inception (2), COLD-PCR has been employed in a variety of applications, including cancer, prenatal diagnostics, infectious diseases, and crop development (3). In COLD-PCR, mutation-containing sequences are enriched either because they have reduced melting temperatures ( T m) due to the type of mutations present (fast-COLD-PCR) or because they form heteroduplexes with wild-type DNA (full-COLD-PCR). In both cases the resulting T m difference is exploited for preferential denaturation and replication of mutated sequences by employing a critical denaturation temperature ( T c) for a given DNA sequence. The T c of an amplicon usually lies approximately 1 °C below the melting temperature ( T m) (4, 5). Because the critical denaturation temperature needs to be controlled precisely during PCR, a thermocycler with a high degree of accuracy and precision in temperature control is desirable, i.e., to within about ±0.2 °C. Unfortunately, this excludes several commonly used PCR machines. For example, the ECO real-time PCR machine from Illumina and the Lightcycler 1536 real-time PCR system from Roche are programmable to 1 °C increments, and the temperature of …
An EMG-based finite state approach for a microcomputer-controlled above-knee prosthesis (2002)

A novel self-contained microcomputer-controlled above-knee prosthesis (AKP) has been developed. The knee mechanism is equipped with a magnetic particle brake providing a continuously variable resistive moment. Several sensors measure the contact pressure under the prosthetic foot, the knee angle and EMG-signals from the stump muscles. This information enables the microcomputer to adjust the braking moment automatically depending on gait mode, gait velocity and other locomotion requirements. The control action is based on a finite state representation of the gait cyclus.
Monoclonal antibody-based therapies for hematologic malignancies. (1998)

Although significant research is still needed, MoAb-based therapies promise to offer new options for the treatment of patients with hematologic malignancies.
Production and characterization of anti‐(mucin MUC1) single‐domain antibody in tobacco (Nicotiana tabacum cultivar Xanthi) (2007)

Members of the Camelidae (camels, dromedaries, llamas, alpacas, guanacos and vicunas) are known to produce Igs (immunoglobulins) devoid of light chains and CH1s (constant heavy-chain domains). The antigen-specific binding fragments of these heavy-chain antibodies therefore comprise one single domain (the so-called 'VHH') and are of great importance in biotechnological applications. To evaluate the expression and biological activity of sdAbs (single-domain antibodies) in plants, which, on account of their small size and antigen-recognition properties, would have a major impact on antibody-engineering strategies, we constructed a pBI121-VHH gene encoding the recombinant sdAb fragments with specificity for a cancer-associated mucin, MUC1. Analysis of transgenic tobacco (Nicotiana tabacum cultivar Xanthi) plants by PCR and Western blotting demonstrated the expression of sdAb, while ELISA results with various MUC1 antigens and immunocytochemistry with cancerous cell lines confirmed that the activity of these molecules compared favourably with that of the parent recombinant antibodies. Protein purification was achieved by using sequential (NH4)2SO4 precipitation, gel filtration and immunoaffinity chromatography. Analysis of the purified VHH by ELISA indicated that the purified antibody fragments were able to react successfully with a MUC1-related peptide. These results reaffirm that the tobacco plant is a suitable host for the production of correctly folded VHH antibody fragments with diagnostic and therapeutic applications.
Detection and Segmentation of 2D Curved Reflection Symmetric Structures (2015)

Symmetry, as one of the key components of Gestalt theory, provides an important mid-level cue that serves as input to higher visual processes such as segmentation. In this work, we propose a complete approach that links the detection of curved reflection symmetries to produce symmetry-constrained segments of structures/regions in real images with clutter. For curved reflection symmetry detection, we leverage on patch-based symmetric features to train a Structured Random Forest classifier that detects multiscaled curved symmetries in 2D images. Next, using these curved symmetries, we modulate a novel symmetry-constrained foreground-background segmentation by their symmetry scores so that we enforce global symmetrical consistency in the final segmentation. This is achieved by imposing a pairwise symmetry prior that encourages symmetric pixels to have the same labels over a MRF-based representation of the input image edges, and the final segmentation is obtained via graph-cuts. Experimental results over four publicly available datasets containing annotated symmetric structures: 1) SYMMAX-300 [38], 2) BSD-Parts, 3) Weizmann Horse (both from [18]) and 4) NY-roads [35] demonstrate the approach's applicability to different environments with state-of-the-art performance.
Comparative studies of speech processing strategies for cochlear implants (1988)

A wide variety of speech processing strategies for multichannel auditory prostheses were compared in studies of two patients implanted with the UCSF electrode array. Each strategy was evaluated using tests of vowel and consonant confusions, with and without lipreading. Included among the strategies were the compressed analog processor of the present UCSF/Storz prosthesis and a group of interleaved pulses processors in which the amplitudes of nonsimultaneous pulses code the spectral variations of speech. For these patients, each with indications of poor nerve survival, test scores were significantly higher with the interleaved pulses processors. We believe this superior performance was a result of 1. the substantial release from channel interactions provided by nonsimultaneous stimuli and 2. a fast enough rotation among the channels to support adequate temporal and spectral resolution of perceived speech sounds.
Lyme Disease (1989)

Within the last decade, Lyme borreliosis has emerged as a complex new infection whose distribution is worldwide. The disorder is caused by a recently recognized spirochete, B. burgdorferi, transmitted by ticks of the I. ricinus complex. Certain species of mice are critical in the life cycle of the spirochete, and deer appear to be crucial to the tick. Although the disorder's basic outlines are similar everywhere, there are regional variations in the causative spirochete, animal hosts, and clinical manifestations of the illness. In the United States, Lyme disease commonly begins in summer with a characteristic skin lesion, erythema migrans, accompanied by flu-like or meningitis-like symptoms. Weeks or months later, the patients may have neurologic or cardiac abnormalities, migratory musculoskeletal pain, or arthritis, and more than a year after onset, some patients have chronic joint, skin, or neurologic abnormalities. After the first several weeks of infection, almost all patients have a positive antibody response to the spirochete, and serologic determinations are currently the most practical laboratory aid in diagnosis. Treatment with appropriate antibiotics is usually curative, but longer courses of therapy are often needed later in the illness, and some patients may not respond.
Exploration of deep intraterrestrial microbial life: current perspectives (2000)

Intraterrestrial life has been found at depths of several thousand metres in deep sub-sea floor sediments and in the basement crust beneath the sediments. It has also been found at up to 2800-m depth in continental sedimentary rocks, 5300-m depth in igneous rock aquifers and in fluid inclusions in ancient salt deposits from salt mines. The biomass of these intraterrestrial organisms may be equal to the total weight of all marine and terrestrial plants. The intraterrestrial microbes generally seem to be active at very low but significant rates and several investigations indicate chemolithoautotrophs to form a chemosynthetic base. Hydrogen, methane and carbon dioxide gases are continuously generated in the interior of our planet and probably constitute sustainable sources of carbon and energy for deep intraterrestrial biosphere ecosystems. Several prospective research areas are foreseen to focus on the importance of microbial communities for metabolic processes such as anaerobic utilisation of hydrocarbons and anaerobic methane oxidation.
Application of metalated enamines to alkaloid synthesis. An expedient approach to the synthesis of morphine-based analgesics (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTApplication of metalated enamines to alkaloid synthesis. An expedient approach to the synthesis of morphine-based analgesicsD. A. Evans, C. H. Mitch, R. C. Thomas, D. M. Zimmerman, and R. L. RobeyCite this: J. Am. Chem. Soc. 1980, 102, 18, 5955–5956Publication Date (Print):August 1, 1980Publication History Published online1 May 2002Published inissue 1 August 1980https://pubs.acs.org/doi/10.1021/ja00538a065https://doi.org/10.1021/ja00538a065research-articleACS PublicationsRequest reuse permissionsArticle Views1048Altmetric-Citations73LEARN 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
Probes for Narcotic Receptor-Mediated Phenomena. 20. Alteration of Opioid Receptor Subtype Selectivity of the 5-(3-Hydroxyphenyl)morphans by Application of the Message-Address Concept: Preparation of .delta.-Opioid Receptor Ligands (1995)

Derivatives of racemic and optically active 5-(3-hydroxyphenyl)-2-methylmorphan (5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1) were synthesized containing additional aromatic moieties, as an application of the message-address concept targeted at producing delta-opioid receptor selective ligands. In vitro radioreceptor binding studies in rat brain revealed that both of the parent enantiomers, (-)- and (+)-1, had a high affinity for the mu-opioid receptor (21 nM), a slight affinity for kappa 1-opioid receptors (approximately 800-900 nM), and less than 1000 nM affinity for the delta-opioid receptor (mu/delta IC50 ratio of < 0.02 for both). A derivative of (-)-1 containing an indole moiety fused at the C6-C7 position of the phenylmorphan nucleus, (-)-11, displayed a > 180-fold increase in affinity for the delta-opioid receptor with an IC50 value of 6 nM. The parent compound (-)-1 had only 26% agonist activity at 30 microM in the mouse vas deferens (delta) bioassay, whereas compound (-)-11 had an IC50 of 393 nM in this preparation, indicating the importance of the indole moiety in imparting delta-opioid agonist activity to the phenylmorphan (-)-11. A structure-activity relationship (SAR) study of N-alkyl derivatives of the racemic nor 11 indicated similarities between the interaction of various derivatives with the mu- and delta- but not the kappa 1-opioid receptor. As studies on the molecular basis of the interaction of opioid ligands with their respective receptors continue to gain momentum, the SAR data described herein for the synthetic phenylmorphans will prove useful for further studies.
Strontium Is a Potent and Selective Inhibitor of Sensory Irritation (1999)

Strontium salts represent a new class of selective inhibitors of sensory irritation and irritant dermatitis.
Necrotizing Pancreatitis: Pathophysiology, Diagnosis, and Acute Care Management (1999)

Severe acute necrotizing pancreatitis is a disease that is caused by premature activation of pancreatic enzymes. Cytokine release contributes to systemic manifestations such as systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), adult respiratory distress syndrome (ARDS), and sepsis. Diagnosis is based on a history of abdominal pain, laboratory values such as serum amylase and lipase levels, and CT scan. Medical management focuses on fluid and electrolyte balance, antibiotic therapy, pain control, and decreasing systemic complications. Surgery is indicated when infectious pancreatic necrosis has been identified. This article addresses incidence and etiology; pathophysiology; clinical manifestations; diagnostics; and medical and surgical patient care management.
A Linkage Map of Sweet Cherry Based on RAPD Analysis of a Microspore-Derived Callus Culture Population (1996)

A partial linkage map was constructed for the sweet cherry (Prunus avium L.) cultivar Emperor Francis from a population of 56 microspore-derived callus culture individuals. The callus cultures were genotyped for two allozymes and 90 random amplified polymorphic DNA (RAPD) markers using 79 random decanucleotide DNA primers and the polymerase chain reaction (PCR). Eighty-nine markers mapped to 10 linkage groups totaling 503.3 cM. DNA blot and hybridization analysis using five cloned RAPDs as probes demonstrated that one of the decanucleotide primers amplified a region of the Emperor Francis genome containing a unique sequence, whereas the other four decanucleotide primers amplified regions of the Emperor Francis genome containing repeated sequences. The five cloned RAPD probes also recognized putative homologous regions in ground cherry, P.fruticosa Pall., and sour cherry, P. cerasus L., a naturally occurring allopolyploid between P.fruticosa and P.avium.
Expression of two soybean vegetative storage protein genes during development and in response to water deficit, wounding, and jasmonic acid. (1990)

The expression of vspA and vspB genes encoding soybean vegetative storage proteins was studied during seedling development and in response to water deficit, tissue wounding, and jasmonic acid treatment. vspA and vspB encode VSP-alpha and VSP-beta, 28-kilodalton and 31-kilodalton vacuole-localized polypeptides that are 80% homologous. vspA and vspB mRNAs could be distinguished on RNA blots using 3'-end probes. vspA mRNA was threefold to sevenfold more abundant than vspB mRNA in leaves, about equal expression was observed in stems, and vspB mRNA exceeded vspA in roots. Transcripts were not detected in dry seeds but appeared in intact or excised seedling axes between 12 hr and 24 hr after initiation of imbibition. Both transcripts were highly abundant in the meristematic region of seedling stems and in developing leaves but were rare in mature stems, leaves, and roots. In situ localization showed that vsp transcripts were found throughout the hypocotyl hook but were concentrated in cells associated with the epidermis and vascular bundles. Water deficit caused increased vsp mRNA levels in leaves and stems, which suggests that inhibition of growth necessitates temporary storage of amino acids. Wounding induced primarily vspB mRNA in etiolated seedlings, whereas both vspA and vspB mRNA levels increased in wounded leaves. Jasmonic acid and methyl jasmonate were potent inducers of vsp gene expression in cell cultures, developing axes, leaves, and roots. We hypothesize that jasmonic acid levels modulate vsp mRNA abundance in vivo.
An A + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. (1991)

Transient expression of some proto-oncogenes, cytokines, and transcription factors occurs as a cellular response to growth factors, 12-O-tetradecanoylphorbol-13-acetate, antigen stimulation, or inflammation. Expression of these genes is mediated in part by the rapid turnover of their mRNAs. A + U-rich elements in the 3' untranslated regions of these mRNAs serve as one recognition signal targeting the mRNAs for rapid degradation. I report the identification of a cytosolic factor that both binds to the proto-oncogene c-myc A + U-rich element and specifically destabilizes c-myc mRNA in a cell-free mRNA decay system which reconstitutes mRNA decay processes found in cells. Proteinase K treatment of the factor abolishes its c-myc mRNA degradation activity without affecting its RNA-binding capacity. Thus, RNA substrate binding and degradation appear to be separable functions. These findings should aid in understanding how the cell selectively targets mRNAs for rapid turnover.
Subtractive immunization yields monoclonal antibodies that specifically inhibit metastasis (1993)

Subtractive immunization allowed the isolation and characterization of monoclonal antibodies that specifically inhibit metastasis but not proliferation of highly metastatic human tumor cells. The tolerizing agent cyclophosphamide was used to suppress the immune system in mice to dominant immunodeterminants present on a non-metastatic variant (M-) of the human epidermoid carcinoma cell line (HEp3). Mice were then inoculated with a highly metastatic variant (M+) of HEp3 to enhance an immune response to antigenic determinants present on metastatic cells. Hybridomas were generated and screened by ELISA for differential reactivity to M+ HEp3 over M- HEp3 cells. This experimental approach, termed subtractive immunization (S.I.), was compared to a control immunization protocol, which eliminated the cyclophosphamide treatment. The S.I. protocol resulted in an eight-fold increase in the proportion of mAbs that react with molecules enriched on the surface of the M+ HEp3 cells. Two of the mAbs derived from the S.I. protocol, designated DM12-4 and 1A5, were purified and examined for their effect in a metastasis model system in which chick embryos are transplanted with primary HEp3 tumors. Purified mAbs DM12-4 and 1A5, inoculated i.v. into the embryos, inhibited spontaneous metastasis of HEp3 cells by 86 and 90%, respectively. The mAbs are specifically anti-metastatic in that they have no effect on the growth of HEp3 cells in vitro nor did they inhibit primary tumor growth in vivo. The mAbs recognize M+ HEp3 cell surface molecules of 55 kD and 29 kD, respectively. These data demonstrate that the S.I. protocol can be used for the development of unique mAbs that are reactive with antigenic determinants whose expression is elevated on metastatic human tumor cells and which function mechanistically in the metastatic cascade.
Development of a metabolically active, non-replicating sporozoite vaccine to preventPlasmodium falciparummalaria (2010)

Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.