gebhart/patrepeval huggingface dataset:
Tradeoffs between the axial resolution and the signal-to-noise ratio in elastography (2002)

Conventional strain estimation techniques in ultrasound-elastography utilize cross-correlation of the pre- and post-compression signals. The quality of the resulting strain estimates is typically quantified through several factors such as the elastographic SNR (SNR/sub e/), the contrast-to-noise ratio (CNR/sub e/), and the spatial resolution. These quality factors depend on the mechanical, acoustic, and signal processing parameters. We find a trade-off between the achievable SNRe (and CNR/sub e/) and the axial resolution. We also find that the trade-off occurs only with respect to the signal processing parameters, while for the physical parameters (the mechanical and the acoustic parameters) such a tradeoff does not exist. Simulations and experiments were used to corroborate this hypothesis.
Diazepam binding inhibitor is a paracrine/autocrine regulator of Leydig cell proliferation and steroidogenesis: action via peripheral-type benzodiazepine receptor and independent mechanisms (1993)

Previous studies demonstrated that the polypeptide diazepam binding inhibitor (DBI) and its receptor, the peripheral-type benzodiazepine receptor (PBR), are involved in the regulation of steroid biosynthesis and that one site of PBR action resides in mitochondria. In the present investigation, evidence is presented that a functional form of PBR is also present at the cell surface. First, PBR was immunolocalized in the rat testis using biotin-streptavidin peroxidase immunocytochemistry, and results revealed that PBR was present exclusively in the interstitial Leydig cells. Next, the distribution of PBR in MA-10 Leydig cells was further examined using confocal microscopy. MA-10 cells were either fixed and immunostained or fixed/permeabilized and immunostained for PBR, followed by generation of confocal microscope optical sections, three-dimensional reconstructions of these sections, and then generation of vertical confocal sections of the three-dimensional reconstruction. In the fixed/unpermeabilized cells, PBR immunostaining at the cell surface was clearly evident, whereas in the fixed/permeabilized cells, intracellular PBR distribution was more robust. These results suggest that the plasma membrane fraction of the receptor could mediate the action of extracellular PBR ligands on Leydig cell function. Next, we examined whether DBI, the naturally occurring PBR ligand, is secreted by testicular cells and whether it could activate the cell surface PBR. Immunolocalization of DBI demonstrated that it was present in both Leydig and Sertoli cells. Further, using an immunoblot assay, we demonstrated that DBI is present in rat testicular interstitial fluid. Metabolic labeling of cultured immature rat Sertoli cells and MA-10 mouse tumor Leydig cells, followed by immunoprecipitation of the secreted proteins with an anti-DBI antiserum, demonstrated that both Leydig and Sertoli cells secrete DBI and could serve as a cell source for the interstitial fluid DBI. Then, we partially purified the DBI present in conditioned medium and interstitial fluid by reverse phase chromatography and demonstrated it to be bioactive, based on displacement of a radiolabeled benzodiazepine (Ro5-4864)-specific ligand for PBR; pronase treatment of different preparations eliminated all bioactivity. We then examined the effects of DBI on Leydig cell function. DBI added to MA-10 cells affected DNA synthesis and cell growth in a biphasic manner; at low concentrations (1 nM), DBI was mitogenic, increasing [3H]thymidine incorporation and cell numbers by 30-40%, while at high concentrations (1 microM), DBI inhibited cell growth (30-40%). Similar effects on cell growth were obtained using the benzodiazepine Ro5-4864.
Visualization and Integrative analysis of cancer multi-omics data (2016)

Understanding and characterizing cancer heterogeneity not only generates new mechanistic insights but can also lead to personalized treatments for patients.With advances in data generation technologies, ever-increasing amounts and types of multiomics open great opportunities for researchers to gain extremely valuable information for cancer research and clinical biomarker discovery.However, the vast and complex nature of multi-omics data pose significant challenges regarding the extraction of useful information and the effective integration of multiple types of data.This dissertation tackles the problem of multi-omics data analysis through both visual analytics and computational angles.First, we present GRAPh based Histology Image Explorer (GRAPHIE ), a visual analytics tool designed to explore, annotate, and discover potential relationships in phenomics datasets (histology images).By taking a data-driven approach, we developed an unbiased way to visualize the entire dataset with node-link graphs.The intuitive visualization and rich set of interactive functions allow users to effectively explore the dataset.While (GRAPHIE ) focusing on analysising the histological information, we present the second visual analytics tool, integrative Genomic Patient Stratification explorer (iGPSe) which leverages multiple types of molecular features to further characterize patients and tumors.iGPSe is designed to assist researchers in effectively performing integrative multi-omics analysis through interactive visualization components.The tool integrates unsupervised
A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells (2005)

This study focused on the screening of small-molecule inhibitors that target signal transducers and activators of transcription 3 (Stat3) in human breast carcinoma. The constitutive activation of Stat3 is frequently detected in human breast cancer cell lines as well as clinical breast cancer specimens and may play an important role in the oncogenesis of breast carcinoma. Activated Stat3 may participate in oncogenesis by stimulating cell proliferation, promoting tumor angiogenesis, and resisting apoptosis. Because a variety of human cancers are associated with constitutively active Stat3, Stat3 represents an attractive target for cancer therapy. In this study, of the nearly 429,000 compounds screened by virtual database screening, chemical samples of top 100 compounds identified as candidate small-molecule inhibitors of Stat3 were evaluated by using Stat3-dependent luciferase reporter as well as other cell-based assays. Through serial functional evaluation based on our established cell-based assays, one compound, termed STA-21, was identified as the best match for our selection criteria. Further investigation demonstrated that STA-21 inhibits Stat3 DNA binding activity, Stat3 dimerization, and Stat3-dependent luciferase activity. Moreover, STA-21 reduces the survival of breast carcinoma cells with constitutive Stat3 signaling but has minimal effect on the cells in which constitutive Stat3 signaling is absent. Together, these results demonstrate that STA-21 inhibits breast cancer cells that express constitutively active Stat3.
Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. (1980)

A preliminary serotherapeutic trial was undertaken with a monoclonal antibody designated antibody 89 (Ab 89) directed against a lymphoma-associated antigen. In vitro studies demonstrated that Ab 89 could mediate complement-dependent lysis and macrophage adherence but not antibody-dependent cell-mediated cytotoxicity. To evaluate toxicity and therapeutic efficacy, two courses of Ab 89 were administered to a patient with an Ab 89-reactive tumor. Transient decreases in the number of circulating tumor cells and the appearance of circulating dead cells were noted with the infusion of Ab 89. Following administration of 150 mg or more of Ab 89, small amounts of antibody could be demonstrated on circulating tumor cells at a time when no free antibody was found in the serum. The inability to deliver a significant amount of Ab 89 to tumor cells in vivo is thought to be secondary to a circulating tumor antigen. Following each infusion, the amount of this blocking antigen decreased but could not be entirely cleared from the serum. This study provides preliminary evidence for the lack of clinical toxicity of a monoclonal antibody and identifies circulating blocking antigens as a significant obstacle to serotherapy.
Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population (1992)

The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.
Production and Molecular Characterization of Clinical Phase I Anti-Melanoma Mouse IgG3 Monoclonal Antibody R24 (2001)

R24 is a mouse IgG3 monoclonal antibody (mab) that reacts with the ganglioside GD3 expressed by cells of neuroectodermal origin. The anti-tumor activity of R24 has been demonstrated in initial phase I and pilot trials in patients suffering from metastatic melanoma. The purpose of this study was to investigate the biotechnological production and particularly the glycosylation of this clinically important antibody. Growth, metabolism, and IgG production of R24 secreting hybridoma cells were analyzed on 1 L bioreactor bench scale using repeated-batch mode. The amount of 57 mg of pure mab was obtained from 1.6 L crude supernatant by protein A chromatography. Western blot binding assays with sugar-specific lectins revealed glycosylation of the heavy chains, whereas no carbohydrates were detectable on the light chains. Because glycosylation is essential for antibody effector functions in vivo (such as complement fixation or binding to macrophage Fc receptors), mab R24 was subjected to both enzymatic deglycosylation using PNGase F and chemical deglycosylation by hydrazinolysis. Released glycans were structurally characterized by high pH anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD), matrix assisted laser desorption ionization time-of-flight (MALDI-TOF), and electrospray ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometry. Six major biantennary chains of the complex glycosylation phenotype were found with variations in galactosylation and core fucosylation. The predominant N-linked structure, indicating the high degree of agalactosyl glycoforms, was the agalacto biantennary chain with a relative percentage of 57% (51% core-fucosylated, 6% nonfucosylated). The second most abundant oligosaccharide was the monogalacto biantennary chain amounting to 30% (26% core- and 4% nonfucosylated). The antibody contained 0.46 microg sialic acid per mg protein, which splits into 0.243 microg Neu5Gc and 0.217 microg Neu5Ac, corresponding to a Neu5Ac:Neu5Gc ratio of 1:1.06. Furthermore, the antigen specificity of R24 was determined by immunodetection of GD3 on thin-layer chromatograms, and real time GD3-antibody binding interactions were measured with an optical biosensor (BIAcore). From the structural data obtained in this study it is concluded that glycosylation of the antibody may be important in the clinical outcome of targeted anti-cancer immunotherapy.
Remote Ischemic Preconditioning for Renal and Cardiac Protection During Endovascular Aneurysm Repair: A Randomized Controlled Trial (2009)

Remote preconditioning reduces urinary biomarkers of renal injury in patients undergoing elective EVAR. This small pilot trial was unable to detect an effect on clinical endpoints; further trials are warranted.
Escherichia coli single-stranded DNA-binding protein mediates template recycling during transcription by bacteriophage N4 virion RNA polymerase (2003)

Coliphage N4 virion RNA polymerase (vRNAP), the most distantly related member of the T7-like family of RNA polymerases, is responsible for transcription of the early genes of the linear double-stranded DNA phage genome. Escherichia coli single-stranded DNA-binding protein (EcoSSB) is required for N4 early transcription in vivo, as well as for in vitro transcription on super-coiled DNA templates containing vRNAP promoters. In contrast to other DNA-dependent RNA polymerases, vRNAP initiates transcription on single-stranded, promoter-containing templates with in vivo specificity; however, the RNA product is not displaced, thus limiting template usage to one round. We show that EcoSSB activates vRNAP transcription at limiting single-stranded template concentrations through template recycling. EcoSSB binds to the template and to the nascent transcript and prevents the formation of a transcriptionally inert RNA:DNA hybrid. Using C-terminally truncated EcoSSB mutant proteins, human mitochondrial SSB (Hsmt SSB), phage P1 SSB, and F episome-encoded SSB, as well as a Hsmt-EcoSSB chimera, we have mapped a determinant of template recycling to the C-terminal amino acids of EcoSSB. T7 RNAP contains an amino-terminal domain responsible for binding the RNA product as it exits from the enzyme. No sequence similarity to this domain exists in vRNAP. Hereby, we propose a unique role for EcoSSB: It functionally substitutes in N4 vRNAP for the N-terminal domain of T7 RNAP responsible for RNA binding.
Autoantibodies to double-stranded (ds)DNA immunoprecipitate 18S ribosomal RNA by virtue of their interaction with ribosomal protein S1 and suppress in vitro protein synthesis (1996)

We report that four systemic lupus erythematosus (SLE) patient sera containing anti-dsDNA antibodies, three affinity-purified anti-dsDNA IgG, and a human anti-dsDNA MoAb (33.H11) immunoprecipitate 18S ribosomal RNA from DNase-treated 32P-labelled MOLT4 cell extract. This 18S RNA precipitation was inhibited completely by preincubating 33.H11 with calf thymus dsDNA or the recombinant human ribosomal protein S1, which was reported to cross-react with anti-dsDNA antibodies (J Immunol 1996; 156:1668-75). Whole IgG from three SLE sera with anti-dsDNA antibodies, 33.H11, and three affinity-purified anti-dsDNA IgG inhibited in vitro translation of globin mRNA (percent inhibition was 36-50%). This translation inhibition by anti-dsDNA antibodies was enhanced (67-79%) when the reticulocyte lysate was treated with DNase. Suppression of protein synthesis could be a pathogenic mechanism of anti-dsDNA antibodies, since it has also been shown that anti-dsDNA penetrates living cells (J Immunol 1995; 154:4857-64) in culture.
Well-Defined Amphiphilic Double-Brush Copolymers and Their Performance as Emulsion Surfactants (2012)

Amphiphilic double-brush copolymers (DBCs) with each graft site quantitatively carrying both a hydrophilic poly(ethylene oxide) (PEO) graft and a hydrophobic polylactide (PLA) graft were synthesized, characterized, and further utilized as surfactants for the stabilization of miniemulsions. Well-defined PEO-b-PLA-based diblock macromonomers (MMs) with exo-norbornene (NB)-functionalized diblock junction were prepared by the synthesis of a PEO-based NB-functionalized alcohol via polymeric reaction, followed by ring-opening polymerization (ROP) of lactide (LA) initiated by the alcohol. Ring-opening metathesis polymerization (ROMP) of the MMs yielded DBCs. The well-controlled structures of the MMs and the DBCs were verified through rigorous instrumental characterizations. As compared with the MMs, the corresponding DBCs had lower crystallinities and melting temperatures (Tms) for both PEO and PLA phases and showed a negligible tendency for intermolecular self-assembly in solutions. With nanoscopic dimensions and novel amphiphilic architectures, these DBCs represent a new type of giant polymeric surfactant. Relative to the precursor MMs, the DBCs resulted in miniemulsions with remarkably enhanced stability.
Synthesis and structure of prolinal-containing peptides, and their use as specific inhibitors of prolyl endopeptidases. (1986)

Peptide aldehydes are potent inhibitors of serine and cysteine proteases. In the present work, N-benzyloxycarbonyl (Z) dipeptides containing prolinal at the carboxyl terminus were syntheized as inhibitors of prolyl endopeptidases. Since no aldehyde proton was detected by proton nuclear magnetic resonance (1H-NMR) spectrometry, a cyclic structure was proposed for these peptides. Compounds with a Z-L-X-L-prolinal structure were strong inhibitors of prolyl endopeptidases from the ascidian, Halocynthia roretzi, and Flavobacterium meningosepticum. The potency was in the order of Z-L-Val-L-prolinal&sime;Z-L-Ile-L-prolinal>Z-L-Phe-L-prolinal>Z-L-Ala-L-prolinal with IC50 values of 10-8-10-6 M order for both enzymes. Conversion of the aldehyde into an alcohol or an acid moiety resulted in a considerable decrease in the inhibitory activity. The diastereomers of Z-L-Phe-L-prolinal were much less inhibitory. This result is not compatible with the reported stereospecifity of the Flavobacterium enzyme for its substrated [T. Yoshimoto, R. Walter and D. Tsuru, J. Biol. Chem., 255, 4786 (1980)]. This implies that the open species binds preferentially to the enzyme active site.
Efficacy of foam liner in 10% carbamide peroxide bleaching technique. (1993)

The purpose of this study was to determine if the use of a foam liner in a tray during the nightguard vital bleaching technique would cause a difference in the rate of bleaching or the final shade of the bleached teeth. Ten subjects were selected who had previously successfully bleached their maxillary arch by using a 10% carbamide peroxide solution. Vacuum-formed guards were fabricated for the mandibular arch so that one quadrant was covered with a conventional-style guard, and the other quadrant was covered with a foam-lined guard. All patients were successful in bleaching their mandibular arch. No patient reported any difference between the two quadrants in the rate of bleaching or in the final shade, nor was any difference apparent to the operators clinically or in photographic evaluation. It appears that the addition of a foam insert does not noticeably alter the clinical result of home bleaching. If bleaching is successful in one arch, it can be expected to be effective in the other arch.
Desktop Growth of Carbon‐Nanotube Monoliths with In Situ Optical Imaging (2007)

Fruits of the forest: A desktop reactor rapidly grows forests of aligned carbon nanotubes (CNTs) to heights of many millimeters by atmospheric-pressure chemical vapor deposition (see picture). This low-cost apparatus achieves the reaction temperature by resistive heating of a suspended silicon platform, and achieves a 20-fold increase in CNT growth rate by thermal pretreatment of the reactant mixture. The film thickness is monitored in situ. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2296/2007/z600716_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Deep brain stimulation of the subthalamic nucleus: model-based analysis of the effects of electrode capacitance on the volume of activation (2005)

Deep brain stimulation (DBS) has rapidly emerged as an effective clinical treatment for movement disorders. However, our understanding of the neural effects of DBS is limited, and significant opportunities exist to optimize electrode design to enhance therapeutic effectiveness. To address these issues, we have developed computational tools to predict the neural response to stimulation. For decades the electrostatic approximation has been applied in neural stimulation modeling, treating the electrode as a perfect current source and the neural tissue as a purely conductive medium. However, clinical DBS electrodes are voltage controlled, utilize an asymmetrical biphasic stimulus waveform, and are surrounded by a 3D anisotropic, inhomogeneous tissue medium. To more accurately model DBS in the human, we have developed finite element models (FEM) of the electrode and tissue medium that incorporate a Fourier FEM solver to determine the potential distribution in the tissue in time and space simultaneously. The field data is then coupled to multi-compartment neuron models to predict neural activation. Our results show that electrostatic models overestimate the volume of activation (VOA) by -30% compared to voltage-controlled stimulation for typical therapeutic stimulation parameter settings. The error is directly related to the electrode capacitance and the stimulation pulse width. These results illustrate the need for detailed models of neural stimulation to accurately predict the effects of DBS
Command and Control Architectures for Autonomous Micro-Robotic Forces - FY-2000 Project Report (2001)

Advances in Artificial Intelligence (AI) and micro-technologies will soon give rise to production of large-scale forces of autonomous micro-robots with systems of innate behaviors and with capabilities of self-organization and real world tasking. Such organizations have been compared to schools of fish, flocks of birds, herds of animals, swarms of insects, and military squadrons. While these systems are envisioned as maintaining a high degree of autonomy, it is important to understand the relationship of man with such machines. In moving from research studies to the practical deployment of large-scale numbers of robots, one of critical pieces that must be explored is the command and control architecture for humans to re-task and also inject global knowledge, experience, and intuition into the force. Tele-operation should not be the goal, but rather a level of adjustable autonomy and high-level control. If a herd of sheep is comparable to the collective of robots, then the human element is comparable to the shepherd pulling in strays and guiding the herd in the direction of greener pastures. This report addresses the issues and development of command and control for largescale numbers of autonomous robots deployed as a collective force.