gebhart/patrepeval huggingface dataset:
Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer (2007)

Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites. POU5F1 (OCT4)-binding site linked to SP1-binding site within the 5'-promoter region of human FZD5 gene was evolutionarily conserved among mammalian FZD5 orthologs. POU5F1 was more related to POU2F and POU3F subfamily members. POU5F1 was preferentially expressed in undifferentiated human embryonic stem (ES) cells, pancreatic islet, and diffuse-type gastric cancer. POU2F1 (OCT1) was expressed in ES cells, fetal liver/spleen, adult colon, POU2F2 in ES cells, fetal liver/spleen, and POU2F3 in diffuse-type gastric cancer. Multiple SP1/KLF family members, other than KLF2 or KLF4, were expressed in undifferentiated human ES cells. Together, these facts indicate that POU5F1 and POU2F subfamily members play a pivotal role for the FZD5 expression in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer.
Fully automated reconstruction of three-dimensional vascular tree structures from two orthogonal views using computational algorithms and productionrules (1992)

A system for reconstructing 3-D vascular structures from two orthogonally projected images is presented. The formidable problem of matching segments between two views is solved using knowledge of the epipolar constraint and the similarity of segment geometry and connectivity. The knowledge is represented in a rule-based system, which also controls the operation of several computational algorithms for tracking segments in each image, representing 2-D segments with directed graphs, and reconstructing 3-D segments from matching 2-D segment pairs. Uncertain reasoning governs the interaction between segmentation and matching; it also provides a framework for resolving the matching ambiguities in an iterative way. The system was implemented in the C Ianguage and the C Language Integrated Production System (CLIPS) expert system shell. Using video images of a tree model, the standard deviation of reconstructed centerlines was estimated to be 0.8 mm (1.7 mm) when the view direction was parallel (perpendicular) to the epipolar plane. Feasibility of clinical use was shown using x-ray angiograms of a human chest phantom. The correspondence of vessel segments between two views was accurate. Computational time for the entire reconstruction process was under 30 s on a workstation. A fully automated system for two-view reconstruction that does not require the <i>a priori</i> knowledge of vascular anatomy is demonstrated.
Expression of a functional human insulin receptor from a cloned cDNA in Chinese hamster ovary cells. (1985)

We have placed human insulin receptor cDNA into a vector under the control of the simian virus 40 (SV40) early promoter and tested its function by transient expression in microinjected Xenopus oocytes and by expression in stably transformed CHO cells. The precursor and the alpha and beta subunits of the receptor were detected by immunoprecipitation from extracts of these cells. The human insulin receptor expressed in CHO cells specifically binds 125I-labeled insulin but not insulin-like growth factor I, displays insulin-stimulated autophosphorylation of the beta subunit, and mediates insulin-stimulated 2-deoxyglucose uptake. We conclude that the human insulin receptor is synthesized, processed normally, and functional in this heterologous cell system.
HGF/SF in Angiogenesis (2007)

Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchyme-derived cytokine that stimulates motility and invasiveness of epithelial and cancer cells. These responses are transduced through the c-met proto-oncogene product, a transmembrane tyrosine kinase that functions as the HGF/SF receptor. We have shown that HGF/SF is a potent angiogenic molecule and that its angiogenic activity is mediated primarily through direct actions on vascular endothelial cells. These include stimulation of cell migration, proliferation, protease production, invasion, and organization into capillary-like tubes. We further showed that HGF/SF is overexpressed in invasive human cancers, including breast cancer, relative to non-invasive cancers and benign conditions. In invasive breast cancers, the content of HGF/SF is strongly correlated with that of von Willebrand's factor, a marker of vascular endothelial cells. Furthermore, transfection of breast cancer and glioma cell lines with HGF/SF cDNA greatly enhanced the ability of these cells to grow as tumours in orthotopic sites in syngeneic or immunocompromized host animals. The increased growth rate of the HGF/SF-transfected cells was attributable, in part, to increased tumour angiogenesis. These findings suggest that HGF/SF may function as a tumour progression factor, in part by stimulating tumour cell invasiveness and in part by stimulating angiogenesis.
Cytokine and Chemokine Levels in Coronavirus Disease 2019 Convalescent Plasma (2020)

Heterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.
Monoclonal antibodies against heparin-binding growth factor II/basic fibroblast growth factor that block its biological activity: invalidity of the antibodies for tumor angiogenesis. (1989)

Two monoclonal antibodies (mAbs) against bovine heparin-binding growth factor II (HBGF-II)/basic fibroblast growth factor (bFGF) were obtained from mouse hybridoma cell lines. They were highly specific for bFGF from bovine, human, and mouse sources and did not cross-react with bovine heparin-binding growth factor I (HBGF-I)/acidic fibroblast growth factor (aFGF). The immunoglobulin class and subclass of these mAbs were IgG1, K. The apparent dissociation constant (Kd) for bFGF of these mAbs ranged from 10(-9) to 10(-10) M. One mAb (bFM-2) also cross-reacted with heat-inactivated bFGF, while the other mAb (bFM-1) did not, suggesting that bFM-1 recognized the conformation of the bFGF molecule necessary for its biological activity. These mAbs inhibited growth of cultured bovine capillary endothelial cells in both the presence and absence of exogenous bFGF, indicating the autocrine action of this growth factor in in vitro growth of these cells. On the other hand, injection of these hybridoma cell lines s.c. into the backs of athymic mice resulted in development of highly vascularized solid tumors and a sustained high level of anti-bFGF activity in the blood of the tumor-bearing mice. These findings suggest that bFGF is not essential as an autocrine or paracrine growth factor for angiogenesis in vivo. These mAbs should be useful in further studies on the physiological role and the conformation-function relationship of bFGF because they block its biological activity.
Maternal immunity and antibodies to dengue virus promote infection and Zika virus–induced microcephaly in fetuses (2019)

Zika virus (ZIKV), an emergent flaviviral pathogen, has been linked to microcephaly in neonates. Although the risk is greatest during the first trimester of pregnancy in humans, timing alone cannot explain why maternal ZIKV infection leads to severe microcephaly in some fetuses, but not others. The antigenic similarities between ZIKV and dengue virus (DENV), combined with high levels of DENV immunity among ZIKV target populations in recent outbreaks, suggest that anti-DENV maternal antibodies could promote ZIKV-induced microcephaly. We demonstrated maternal-to-fetal ZIKV transmission, fetal infection, and disproportionate microcephaly in immunocompetent mice. We show that DENV-specific antibodies in ZIKV-infected pregnant mice enhance vertical ZIKV transmission and result in a severe microcephaly-like syndrome, which was dependent on the neonatal Fc receptor, FcRN. This novel immune-mediated mechanism of vertical transmission of viral infection is of special concern because ZIKV epidemic regions are also endemic to DENV.
Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia (2018)

Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N = 145) were at least 65 years old with treatment-naive AML and were ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m<sup>2</sup>, days 1-5, intravenously [IV]) or azacitidine (75 mg/m<sup>2</sup>, days 1-7, IV or subcutaneously). In the expansion, 400 or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR + CRi rate of 73% in the venetoclax 400 mg + HMA cohort. Patients with poor-risk cytogenetics and those at least 75 years old had CR + CRi rates of 60% and 65%, respectively. The median duration of CR + CRi (all patients) was 11.3 months, and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (This trial was registered at www.clinicaltrials.gov as #NCT02203773).
Using Data Independent Acquisition (DIA) to Model High-responding Peptides for Targeted Proteomics Experiments (2015)

Targeted mass spectrometry is an essential tool for detecting quantitative changes in low abundant proteins throughout the proteome. Although selected reaction monitoring (SRM) is the preferred method for quantifying peptides in complex samples, the process of designing SRM assays is laborious. Peptides have widely varying signal responses dictated by sequence-specific physiochemical properties; one major challenge is in selecting representative peptides to target as a proxy for protein abundance. Here we present PREGO, a software tool that predicts high-responding peptides for SRM experiments. PREGO predicts peptide responses with an artificial neural network trained using 11 minimally redundant, maximally relevant properties. Crucial to its success, PREGO is trained using fragment ion intensities of equimolar synthetic peptides extracted from data independent acquisition experiments. Because of similarities in instrumentation and the nature of data collection, relative peptide responses from data independent acquisition experiments are a suitable substitute for SRM experiments because they both make quantitative measurements from integrated fragment ion chromatograms. Using an SRM experiment containing 12,973 peptides from 724 synthetic proteins, PREGO exhibits a 40-85% improvement over previously published approaches at selecting high-responding peptides. These results also represent a dramatic improvement over the rules-based peptide selection approaches commonly used in the literature.
Multidimensional femtosecond spectroscopies of vibrational motions in liquids: Semiclassical expansion (1998)

Fifth- (χ(5)) and seventh- (χ(7)) order electronically off-resonant Raman spectroscopies in molecular liquids are investigated using a new semiclassical expansion of the optical response which applies for weak anharmonicities and low temperatures. The leading contribution can be calculated using classical equations of motion for nuclear wave packets, even when the system itself may be highly nonclassical. Two sources of nonlinearities which generate the signals—the nonlinear dependence of the polarizability on nuclear coordinates and vibrational anharmonicities—are identified. Formal analogy between the present equations and the time-dependent Hartree–Fock equations used in electronic nonlinear spectroscopy suggests specific experimental signatures of the various nonlinearities.
DANN: a deep learning approach for annotating the pathogenicity of genetic variants (2014)

All data and source code are available at https://cbcl.ics.uci.edu/public_data/DANN/.
Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease. (1989)

To assess the relative influence of central pharmacodynamic and peripheral pharmacokinetic factors on the duration of motor response to levodopa, the relationship between motor function and plasma levodopa levels was studied in 31 Parkinsonian patients. Duration of benefit from single levodopa doses while fasting depended on the degree to which the plasma levodopa level had declined over four hours; wearing off occurred when the plasma levodopa level had fallen to approximately 50% of peak concentration, irrespective of the duration of the motor response. Whilst the amplitude of motor response to levodopa is likely to be modified by alternations in dopamine receptor stimulation and sensitivity as the disease progresses, it is proposed that the duration of response is primarily determined by levodopa peripheral pharmacokinetics rather than by central pharmacodynamic factors associated with dopamine storage capacity.
The ankyrin repeat protein Diversin recruits Casein kinase Iε to the β-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling (2002)

Wnt signals control decisive steps in development and can induce the formation of tumors. Canonical Wnt signals control the formation of the embryonic axis, and are mediated by stabilization and interaction of beta-catenin with Lef/Tcf transcription factors. An alternative branch of the Wnt pathway uses JNK to establish planar cell polarity in Drosophila and gastrulation movements in vertebrates. We describe here the vertebrate protein Diversin that interacts with two components of the canonical Wnt pathway, Casein kinase Iepsilon (CKIepsilon) and Axin/Conductin. Diversin recruits CKIepsilon to the beta-catenin degradation complex that consists of Axin/Conductin and GSK3beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals. Morpholino-based gene ablation in zebrafish shows that Diversin is crucial for axis formation, which depends on beta-catenin signaling. Diversin is also involved in JNK activation and gastrulation movements in zebrafish. Diversin is distantly related to Diego of Drosophila, which functions only in the pathway that controls planar cell polarity. Our data show that Diversin is an essential component of the Wnt-signaling pathway and acts as a molecular switch, which suppresses Wnt signals mediated by the canonical beta-catenin pathway and stimulates signaling via JNK.
The Lottery Ticket Hypothesis: Finding Sparse, Trainable Neural Networks. (2019)

Neural network pruning techniques can reduce the parameter counts of trained networks by over 90%, decreasing storage requirements and improving computational performance of inference without compromising accuracy. However, contemporary experience is that the sparse architectures produced by pruning are difficult to train from the start, which would similarly improve training performance. We find that a standard pruning technique naturally uncovers subnetworks whose initializations made them capable of training effectively. Based on these results, we articulate the lottery ticket hypothesis: dense, randomly-initialized, feed-forward networks contain subnetworks (winning tickets) that-when trained in isolation-reach test accuracy comparable to the original network in a similar number of iterations. The winning tickets we find have won the initialization lottery: their connections have initial weights that make training particularly effective. We present an algorithm to identify winning tickets and a series of experiments that support the lottery ticket hypothesis and the importance of these fortuitous initializations. We consistently find winning tickets that are less than 10-20% of the size of several fully-connected and convolutional feed-forward architectures for MNIST and CIFAR10. Above this size, the winning tickets that we find learn faster than the original network and reach higher test accuracy.
Rapid termination of intraoperative stimulation-evoked seizures with application of cold Ringer's lactate to the cortex (1998)

One major risk of intraoperative stimulation mapping is the production of stimulation-evoked seizures. Cold Ringer's lactate solution was applied directly to the irritated cortex in 22 patients with stimulation-induced seizures that occurred during intraoperative brain mapping procedures. The irrigation rapidly and reliably terminated these simple partial seizures and eliminated the need for intravenously administered short-acting barbiturates with antiepileptic properties. The authors describe a practical and simple method for controlling stimulation-induced seizure activity during brain mapping procedures.
Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia. (1985)

Platelets coated with quinine- or quinidine-induced antibodies form rosettes around protein A-Sepharose beads and normal platelets form rosettes about protein A-Sepharose beads coated with these antibodies. These reactions occurred only in the presence of sensitizing drug. Platelets also formed rosettes about protein A-Sepharose beads coated with an anti-PIA1 antibody, but drug was not required. Formation of rosettes between antibody-coated platelets and protein A-Sepharose was inhibited by F(ab')2 fragments of goat antibody specific for the Fc portion of human IgG, while rosette formation between antibody-coated protein A-Sepharose and platelets was inhibited by F(ab')2 fragments directed against the F(ab')2 portion of the IgG molecule. Since binding of IgG to protein A is known to occur via the Fc region, these findings suggest that binding of drug-induced antibodies to platelets occurs at the Fab domains of the IgG molecule.
Safracins,new antitumor antibiotics I. Producing organism,fermentation and isolation. (1983)

Safracins, new antibiotics with a novel skeleton, were discovered in a culture broth of Pseudomonas sp. The producing organism has been identified as Pseudomonas fluorescens. Safracins A and B were isolated by ethyl acetate extraction and chromatography on silica gel.
Cytokine gene polymorphisms and susceptibility to chronic irritant contact dermatitis (2008)

This study provides evidence that some genetic variations alter susceptibility to (chronic) dermatitis. Knowledge of the impact of genetic differences on the risk of CICD is essential in predictive testing of individuals at risk.
Rescue of Recombinant Newcastle Disease Virus from cDNA (2013)

Newcastle disease virus (NDV), the prototype member of the Avulavirus genus of the family Paramyxoviridae(1), is a non-segmented, negative-sense, single-stranded, enveloped RNA virus (Figure 1) with potential applications as a vector for vaccination and treatment of human diseases. In-depth exploration of these applications has only become possible after the establishment of reverse genetics techniques to rescue recombinant viruses from plasmids encoding their complete genomes as cDNA(2-5). Viral cDNA can be conveniently modified in vitro by using standard cloning procedures to alter the genotype of the virus and/or to include new transcriptional units. Rescue of such genetically modified viruses provides a valuable tool to understand factors affecting multiple stages of infection, as well as allows for the development and improvement of vectors for the expression and delivery of antigens for vaccination and therapy. Here we describe a protocol for the rescue of recombinant NDVs.
The effect of conjugation on immunogenicity and potency of protein carriers of polyribosylribitol phosphate (PRP) conjugated vaccines in the mouse model (1998)

Immunogenicity and vaccine potency of carrier proteins of two different PRP-tetanus toxoid (PRP-T) conjugated vaccines, produced using different size PRP (Act-Hib & Amvax Hib-T), and one PRP-CRM197 (Hib-TITER) were studied. The immunogenicity and the vaccine potency of the carrier component of the tested PRP-conjugated vaccines, and their influences on the potency of the tetanus toxoid (T) and of the diphtheria toxoid (D) component of diphtheria toxoid-tetanus toxoid-acellular pertussis-inactivated polio vaccine (DTaP-IPV) were variable. The T component of Act-Hib (large size PRP) was as immunogenic and potent as the T component of the DTaP-IPV vaccine, and a combination of Act-Hib and DTaP-IPV resulted in a more than five-fold increase in the potency of the T However, Amvax Hib-T (small size PRP) did not show any anti-T response on its own, and a combination of Amvax Hib-T and DTaP-IPV did not affect the T potency of the DTaP-IPV vaccine. In immunogenicity studies with multiple shots, Hib-TITER (small size PRP) produced significantly less anti-D antibodies than non-conjugated D. Hib-TITER did not show any D potency on its own, while a combination of a Hib-TITER and DTaP-IPV increased the potency of the D component of DTaP-IPV vaccine significantly. Thus, in the case of a combination of T-and D-containing vaccines with a PRP-conjugated vaccine in which either T or CRMI 97 has been used as the carrier, the influence of these carriers on basic immunogenicity and vaccine potency of T and D, respectively, should be considered carefully. We propose the techniques employed in this study for the quality control of combined vaccines consisting of diphtheria, tetanus, and PRP-conjugated vaccines.