gebhart/patrepeval huggingface dataset:
Absorption and Metabolism of Topically Applied Testosterone in an Organotypic Skin Culture (1992)

The Living Skin Equivalent (LSE) is an organotypic coculture of human dermal fibroblasts in a collagen-containing matrix and a stratified epidermis composed of human epidermal keratinocytes. In order to establish the feasibility of using this in vitro system as a model for cutaneous biotransformation, the metabolic fate of topically applied testosterone (T) was monitored in the LSE. After a 24-hour exposure period (37 degrees C) to radiolabelled T, LSE extracts analyzed by high-performance thin-layer chromatography showed that approximately 50% of the applied T had been metabolized. Identified metabolites included bands which comigrated with polar metabolites and products of T 5 alpha-reductase. The general distribution of the observed metabolites was similar to that obtained using biopsied human skin. The rates of T penetration (32 degrees C) through the LSE were monitored after application of T in two vehicles (water and petrolatum) and yielded permeability constants (Kps) of 29 and 1.6 x 10(-3) cm/h, respectively. These Kp values were 4- to 6-fold higher than those reported for human abdominal skin, and reflect the vehicle-related shift in penetration seen in human skin. The Kp values for two additional steroids, estradiol and hydrocortisone, and for T were also determined at 22 degrees C and compared to published Kp values. These Kp values in the LSE were, respectively, 63-, 187- and 35-fold higher than those reported for human skin. The data suggest that compared to human skin the LSE has only a partial barrier function to the passage of test chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)
RVD: a command-line program for ultrasensitive rare single nucleotide variant detection using targeted next-generation DNA resequencing (2013)

RVD meets a growing need for highly sensitive and specific tools for variant detection. To demonstrate the usefulness of RVD, we carried out a thorough analysis of the software's performance on synthetic and clinical virus samples sequenced on both an Illumina GAIIx and a MiSeq. We expect RVD can improve understanding the genetics and treatment of common viral diseases including influenza. RVD is available at the following URL:http://dna-discovery.stanford.edu/software/rvd/.
Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells (1991)

Murine bone marrow cells expressing the cell surface Ag RB6-8C5 were identified by fluorescence-activated cell-sorting analysis using a rat IgG mAb. The fluorescent intensity of RB6-8C5 was variable on bone marrow cells. This made it possible to separate bone marrow cells into distinct subpopulations, RB6-8C5neg, RB6-8C5lo, and RB6-8C5hi cells. Morphologic analysis of the sorted populations demonstrated that the Ag was expressed on myeloid cells. The expression of RB6-8C5 increases with granulocyte maturation, whereas expression is transient on cells in the monocytic lineage. The RB6-8C5hi sorted cells were enriched for end-stage neutrophils (75%), whereas the RB6-8C5lo sorted cells contained more immature myeloid cells and myelocytes (75%). Lymphocytes and macrophages were less than 5% in any RB6-8C5+ population, whereas the erythroid precursors were RB6-8C5neg. The colony forming unit culture (CFU-C) (greater than 90%) were found in the RB6-8C5neg and RB6-8C5lo populations, and all the CFU-granulocyte, erythroid, megakaryocyte, and macrophage (CFU-GEMM) and burst-forming units-erythroid (BFU-E) were in the RB6-8C5neg population. Granulocyte-macrophage-CSFR (GM-CSFR) and IL-1 alpha R were expressed on RB6-8C5hi bone marrow cells, whereas no receptors could be detected on RB6-8C5neg and RB6-8C5lo cells. The expression of the RB6-8C5 Ag can be induced on RB6-8C5neg cells in liquid culture by IL-3 and granulocyte-macrophage CSF. Thus, RB6-8C5 is a myeloid differentiation Ag whose expression can be regulated by cytokines.
Dual-mode ultrasound phased arrays for imaging and therapy (2005)

We have recently demonstrated the imaging capabilities of a prototype 64-element 1 MHz concave array with 100 mm radius of curvature. This array was optimized for therapeutic applications using high-intensity focused ultrasound (HIFU). We have shown that this dual-mode ultrasound array (DMUA) has a therapeutic operating field (ThxOF) that extends by /spl plusmn/3 cm and /spl plusmn/2 cm around its geometric center in the axial and lateral directions, respectively. We have also shown that appropriate apodization and accounting for element directivity along with conventional synthetic aperture beamforming produce a 50 dB imaging field of view (IxFOV) larger than the ThxOF. In addition, the spatial registration of imaging targets is as accurate as commercially available scanners. In this paper, we present results from an image-based refocusing algorithm whereby images formed by the DMUA are used to identify a refocusing target and a set of critical points where the incident power is to be minimized. The algorithm is validated experimentally in tissue mimicking phantom with strongly scattering ribs placed between the DMUA and the target. These results demonstrate what is potentially the most powerful advantage of the use of DMUAs in image-guided surgery. Namely, the inherent registration between the imaging and therapeutic coordinate systems. This allows for direct definition of targets and any surrounding critical structures to be avoided to minimize the collateral damage. With these capabilities, DMUAs may provide a most powerful paradigm for image-guided surgery.
Local modeling of global interactome networks (2005)

http://daisy.prevmed.northwestern.edu/~denise/pubs/LocalModeling
Tissue-Specific Differences in PD-1 and PD-L1 Expression during Chronic Viral Infection: Implications for CD8 T-Cell Exhaustion (2009)

The PD-1/PD-L pathway plays a major role in regulating T-cell exhaustion during chronic viral infections in animal models, as well as in humans, and blockade of this pathway can revive exhausted CD8(+) T cells. We examined the expression of PD-1 and its ligands, PD-L1 and PD-L2, in multiple tissues during the course of chronic viral infection and determined how the amount of PD-1 expressed, as well as the anatomical location, influenced the function of exhausted CD8 T cells. The amount of PD-1 on exhausted CD8 T cells from different anatomical locations did not always correlate with infectious virus but did reflect viral antigen in some tissues. Moreover, lower expression of PD-L1 in some locations, such as the bone marrow, favored the survival of PD-1(Hi) exhausted CD8 T cells, suggesting that some anatomical sites might provide a survival niche for subpopulations of exhausted CD8 T cells. Tissue-specific differences in the function of exhausted CD8 T cells were also observed. However, while cytokine production did not strictly correlate with the amount of PD-1 expressed by exhausted CD8 T cells from different tissues, the ability to degranulate and kill were tightly linked to PD-1 expression regardless of the anatomical location. These observations have implications for human chronic infections and for therapeutic interventions based on blockade of the PD-1 pathway.
Platelet-derived growth factor receptors expressed by cDNA transfection couple to a diverse group of cellular responses associated with cell proliferation. (1988)

We have expressed the mouse platelet-derived growth factor (PDGF) receptor cDNA under transcriptional control of simian virus 40 promoter in Chinese hamster ovary cells, a cell type that lacks PDGF receptors. Stable transfectants expressed receptor protein that was recognized by antireceptor antibodies. PDGF stimulated a diverse group of responses in the transfected cells including tyrosine phosphorylation of the receptor and a 32-kDa cellular substrate, receptor internalization, phosphoinositide turnover, cytoplasmic alkalinization, changes in the intracellular calcium concentration, thymidine uptake into DNA, and cell division. There were no responses to PDGF in the control Chinese hamster ovary cells. After prolonged exposure to PDGF, the transfectants became refractory to subsequent PDGF stimulation and the receptor protein was no longer detectable. These data validate the authenticity of the PDGF receptor cDNA, show that transfection of a single type of receptor cDNA sequence confers PDGF sensitivity to a diverse group of cellular responses, and demonstrate that effector molecules that mediate the PDGF responses are present in cells that lack PDGF receptors.
Liquid-phase reactions started by rehydrating lyophilized reagents in a centrifugal analyzer. (1985)

In the disposable rotor of the SAM microcentrifugal analyzer, various lyophilized reagents are predistributed in 24 33-microL cuvets, for determination of multiple analytes in one specimen (e.g., for patient profiles). We evaluated a prototype of this system, which can be used at 25, 30, or 37 degrees C; absorbance readings at 340, 405, and 500 nm varied linearly up to 2.0 A. Starting the reactions by rehydrating the reagents with diluted serum is adequate because absorbance readings do not begin until 180 s after initiating the rehydration. Analytical performances of kinetic determinations at 30 degrees C showed good accuracy and correlation with other methods for creatine kinase, amylase, aspartate aminotransferase, and gamma-glutamyltransferase. Kinetic determinations for urea, and equilibrium determinations with blank corrections for glucose, cholesterol, and triglycerides gave excellent results for glucose and correct results for the other analytes. This compact analyzer combines the analytical performances of a centrifugal analyzer with the practicability of instruments having predistributed reagents.
Novel 4-Aminoquinoline-Pyrimidine Based Hybrids with Improved in Vitro and in Vivo Antimalarial Activity (2012)

A class of hybrid molecules consisting of 4-aminoquinoline and pyrimidine were synthesized and tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay. Eleven hybrids showed better antimalarial activity against both CQ-sensitive and CQ-resistant strains of P. falciparum in comparison to standard drug CQ. Four molecules were more potent (7-8-fold) than CQ in D6 strain, and eight molecules were found to be 5-25-fold more active against resistant strain (W2). Several compounds did not show any cytotoxicity up to a high concentration (60 μM), others exhibited mild toxicities, but the selective index for the antimalarial activity was very high for most of these hybrids. Two compounds selected for in vivo evaluation have shown excellent activity (po) in a mouse model of Plasmodium berghei without any apparent toxicity. The X-ray crystal structure of one of the compounds was also determined.
‘Cold SSCP’: a simple, rapid and non-radioactive method for optimized single-strand conformation polymorphism analyses (1993)

A rapid (< 2.5 hrs) method for single-strand conformation polymorphism (SSCP) analysis of PCR products that allows the use of ethidium bromide staining is described. PCR products ranging in size from 117 to 256 bp were evaluated for point mutations and polymorphisms by 'cold SSCP' in commercially available pre-cast polyacrylamide mini-gels. Several electrophoretic parameters (running temperature, buffers, denaturants, DNA concentration, and gel polyacrylamide concentration) were found to influence the degree of strand separation and appeared to be PCR fragment specific. Use of the 'cold' SSCP technique and the mini-gel format allowed us to readily optimize the electrophoretic conditions for each PCR fragment. This greatly increased our ability to detect polymorphisms compared to conventional, radioisotope-labeled 'hot' SSCP, typically run under two standard temperature conditions. Excellent results have been obtained in resolving mutant PCR fragments from human p53 exons 5 through 8, human HLA-DQA, human K-ras exons 1 and 2, and rat K-ras exon 3. Polymorphisms could be detected when mutant DNA comprised as little as 3% of the total gene copies in a PCR mixture. Compared to standard 'hot' SSCP, this novel non-isotopic method has additional advantages of dramatically increased speed, precise temperature control, reproducibility, and easily and inexpensively obtainable reagents and equipment. This new method also lacks the safety and hazardous waste management concerns associated with radioactive methods.
Object Bank: A High-Level Image Representation for Scene Classification & Semantic Feature Sparsification (2018)

Robust low-level image features have been proven to be effective representations for a variety of visual recognition tasks such as object recognition and scene classification; but pixels, or even local image patches, carry little semantic meanings. For high level visual tasks, such low-level image representations are potentially not enough. In this paper, we propose a high-level image representation, called the Object Bank, where an image is represented as a scale-invariant response map of a large number of pre-trained generic object detectors, blind to the testing dataset or visual task. Leveraging on the Object Bank representation, superior performances on high level visual recognition tasks can be achieved with simple off-the-shelf classifiers such as logistic regression and linear SVM. Sparsity algorithms make our representation more efficient and scalable for large scene datasets, and reveal semantically meaningful feature patterns.
The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication but Is Dispensable for Inflammatory Response Signaling (2009)

The innate immune response provides the first line of defense against foreign pathogens by responding to molecules that are a signature of a pathogenic infection. Certain RNA viruses, such as influenza virus, produce double-stranded RNA as an intermediate during the replication life cycle, which activates pathogen recognition receptors capable of inducing interferon production. By engaging interferon receptors, interferon activates the JAK-STAT pathway and results in the positive feedback of interferon production, amplifying the response to viral infection. To examine how deficiencies in interferon signaling affect the cellular response to infection, we performed influenza virus infections of mouse embryonic fibroblasts lacking the alpha/beta interferon receptor, the gamma interferon receptor, or both. In the absence of the alpha/beta interferon receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-kappaB; the presence or absence of the gamma interferon receptor did not exhibit discernible differences in these readouts. Analysis of gene expression profiles showed that while cells lacking the alpha/beta interferon receptor exhibited decreased levels of transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to levels similar to those of cells containing the receptor. These results indicate that while the alpha/beta interferon receptor is needed to curb viral replication, it is dispensable for the induction of certain inflammatory and apoptotic genes. We have identified potential pathways, via interferon regulatory factor 3 (IRF3) activation or Hoxa13, Polr2a, Nr4a1, or Ing1 induction, that contribute to this redundancy. This study illustrates another way in which the host has evolved to establish several overlapping mechanisms to respond to viral infections.
Mehrfunktionelle N‐Tenside. I. Nucleophile Substitutionen an Bischlornitrosoverbindungen. 1. Reaktionen mit Aminen, Mercaptanen und Natriumazid (1978)

Polyfunctionalized N‐Tensides. I. Nucleophilic Substitutions with Bischloronitrosocompounds. 1. Reactions with Amines, Mercaptans and Sodium Azide Chloronitrosation of alkenes gives bischloronitrosocompounds 1 , which react with amines to α‐aminooximes ( 2 and 4 ), with mercaptans to α‐alkylthiooximes 11 , and with sodium azide to α‐azidooximes 8 . Reduction with LiAlH 4 gives vicinal substituted diamines ( 6 , 7 , 10 ) from α‐amino‐or α‐azidooximes ( 2 , 4 , 8 ) and β‐alkylthioamines 13 from α‐alkylthiooximes 11 . The determination of E ‐ or Z ‐configuration in the α‐substituted oximes is discussed.
Identification of Posttranslationally Modified 18-Kilodalton Protein from Rice as Eukaryotic Translation Initiation Factor 5A (1994)

Using anther-derived rice (Oryza sativa L.) cell-suspension cultures, we have identified an 18-kD protein that is posttranslationally modified by spermidine and is influenced by endogenous polyamine levels. The posttranslationally modified residue has been identified as the unusual amino acid hypusine [N[epsilon]-(4-amino-2-hydroxybutyl)lysine] by reverse-phase high-performance liquid chromatography and gas chromatography-mass-spectrometry analyses. Differential labeling of the protein with labeled amines provided evidence that the butylamine moiety of spermidine is the immediate precursor of the hypusine residue in the protein. The eukaryotic translation initiation factor 5A (eIF-5A) is the only known mammalian protein that undergoes a similar posttranslational modification with hypusine. The purified 18-kD protein co-electrophoreses with human translational initiation factor eIF-5A in both isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gels. The purified protein from rice stimulated methionyl-puromycin synthesis in vitro, indicating its functional similarity to mammalian eIF-5A. The results presented provide evidence that the posttranslationally modified 18-kD protein from rice containing hypusine is eIF-5A and suggest the conservation of hypusine-containing translation initiation factor eIF-5A in eukaryotes.
Transferrin/transferrin receptor‐mediated drug delivery (2002)

Since transferrin was discovered more than half a century ago, a considerable effort has been made towards understanding tranferrin-mediated iron uptake. However, it was not until recently with the identification and characterization of several new genes related to iron homeostasis, such as the hemochromatosis protein HFE and the iron transporter DMT1, that our knowledge has been advanced dramatically. A major pathway for cellular iron uptake is through internalization of the complex of iron-bound transferrin and the transferrin receptor, which is negatively modulated by HFE, a protein related to hereditary hemochromatosis. Iron is released from transferrin as the result of the acidic pH in endosome and then is transported to the cytosol by DMT1. The iron is then utilized as a cofactor by heme and ribonucleotide reductase or stored in ferritin. Apart from iron, many other metal ions of therapeutic and diagnostic interests can also bind to transferrin at the iron sites and their transferrin complexes can be recognized by many cells. Therefore, transferrin has been thought as a "delivery system" for many beneficial and harmful metal ions into the cells. Transferrin has also be widely applied as a targeting ligand in the active targeting of anticancer agents, proteins, and genes to primary proliferating malignant cells that overexpress transferrin receptors. This is achieved by conjugation of transferrin with drugs, proteins, hybride systems with marcomolecules and as liposomal-coated systems. Conjugates of anticancer drugs with transferrin can significantly improve the selectivity and toxicity and overcome drug resistance, thereby leading to a better treatment. The coupling of DNA to transferrin via a polycation such as polylysine or via cationic liposomes can target and transfer of the extrogenous DNA particularly into proliferating cells through receptor-mediated endocytosis. These kinds of non-viral vectors are potential alternatives to viral vectors for gene therapy, if the transfection efficiency can be improved. Moreover, transferrin receptors have shown potentials in delivery of therapeutic drugs or genes into the brain across blood-brain barrier.
Molecular Mechanisms of Resistance to Cetuximab and Panitumumab in Colorectal Cancer (2010)

Personalized cancer medicine based on the genetic milieu of individual colorectal tumors has long been postulated, but until recently this concept was not supported by clinical evidence. The advent of the epidermal growth factor receptor (EGFR) -targeted monoclonal antibodies cetuximab and panitumumab has paved the way to the individualized treatment of metastatic colorectal cancer (mCRC). Here we discuss the evidence that mCRCs respond differently to EGFR-targeted agents and that the tumor-specific response has a genetic basis. We outline how, from the initial observation that cetuximab or panitumumab as monotherapy is effective only in 10% to 20% of mCRCs, knowledge has being gained on the molecular mechanisms underlying primary resistance to these agents. The role of oncogenic activation of EGFR downstream effectors such as KRAS, BRAF, PIK3CA, and PTEN on response to therapy is discussed. We suggest that CRCs lacking oncogenic alterations in these four genes have the highest probability of response to anti-EGFR therapies and are defined as "quadruple negative." The rapid and effective translation of these findings into predictive biomarkers to couple EGFR-targeted antibodies to the patients who benefit from them is presented as a paradigm of modern clinical oncology. Finally, unresolved questions such as understanding the molecular basis of response as well the mechanisms of secondary resistance are presented as the future fundamental goals in this research field.
Glucose transporters: Structure, function and consequences of deficiency (2000)

Abstract There are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by one or more of the members of the closely related GLUT family of glucose transporters. The pattern of expression of the GLUT transporters in different tissues is related to the different roles of glucose metabolism in different tissues. Primary defects in glucose transport all appear to be extremely rare and not all possible deficiencies have been identified. Deficiency of the secondary active sodium/glucose transporters result in glucose/galactose malabsorption or congenital renal glycosuriäGLUT1 deficiency produces a seizure disorder with low glucose concentration in cerebrospinal fluid and GLUT2 deficiency is the basis of the Fanconi–Bickel syndrome, which resembles type I glycogen storage disease.