gebhart/patrepeval huggingface dataset:
Transformation of human granulosa cells with the E6 and E7 regions of human papillomavirus. (1994)

Ovarian granulosa cells are the primary site of estrogen and progesterone synthesis and play an essential role in the maturation of the developing ovum. Freshly isolated granulosa cells are often used to study the regulation of steroid and protein biosynthesis, but the small number of cells available for these cultures has proven inadequate for many detailed gene regulatory studies. The goal of this study was to develop human granulosa (HG) cell lines that maintain differentiated function. The E6 and E7 open reading frames of high risk strains of human papillomavirus have been used to produce immortalized cell lines. Primary cultures of human luteinized granulosa cells were infected with defective retroviruses containing the E6 and E7 regions of human papillomavirus 16 and with the neomycin phosphotransferase gene to confer G418 resistance. Three of eight clones that were isolated after selection in medium containing G418 were found to produce progesterone following treatment with forskolin or dibutyryl cAMP for 48 h. Forskolin caused these cells to retract in the characteristic rounding response, as described in primary HG cultures. One clone, HGL5, was used for a detailed characterization of differentiated function. HGL5 cells retained the ability to increase progesterone production and convert exogenously added androstenedione to estradiol in response to agonists of the protein kinase-A pathway (forskolin and dibutyryl cAMP), but were not responsive to FSH or LH treatment. A key enzyme in the production of estradiol, cytochrome P450 aromatase, has proven difficult to maintain in long term cultures of granulosa cells. For that reason, we examined the expression of aromatase in the transformed HGL5 clone by monitoring mRNA levels. Aromatase mRNA increased by 4- to 5-fold after forskolin treatment, as determined by Northern analysis. This human granulosa cell culture line maintains many of the functions of normal cells and should provide an important model to study the molecular events controlling granulosa cell differentiation and function.
<title>High-resolution parallel optical coherence tomography in scattering samples</title> (2001)

Parallel optical coherence tomography in scattering samples is demonstrated using a 58 by 58 smart-pixel detector array. A femtosecond mode-locked Ti:Sapphire laser in combination with a free space Michelson interferometer was employed to achieve 4micrometers longitudinal resolution and 9mm transverse resolution on a 260x260 micrometers <SUP>2</SUP> field of view. We imaged a resolution target covered by an intralipid solution with different scattering coefficients as well as onion cells.
II. Dynamic and crystallographic analysis (1987)

Abstract Dislocation transmission through a (122), ∑ = 9 boundary in Ge or Si is first studied from the crystallographic point of view. Grain-boundary structure alterations induced by transmission reactions suggested by experimental observations are investigated. The Burgers vectors of extrinsic grain-boundary dislocations and their associated steps are determined. A possible transmission process, which accounts for lattice dislocation dissociation, i.e. transmission of the leading Shockley partial without constriction, is discussed. The strain transmission is also examined using calculations of internal shear stresses exerted by dislocation pileups, in one crystal, at the interface, on all the second crystal's slip systems. Interpretation of the observed transmission reactions is attempted by combining the crystallographic and the dynamic criteria.
Bromocontryphan:  Post-Translational Bromination of Tryptophan (1997)

We demonstrate that post-translational bromination of a tryptophan residue occurs in the biologically active octapeptide bromocontryphan, purified and characterized from Conus radiatus venom. Clones encoding bromocontryphan were identified from a cDNA library made from C. radiatus venom ducts. The mRNA sequence obtained predicts a prepropeptide which has the mature peptide sequence at the C-terminal end, with the L-6-bromotryptophan residue encoded by UGG, the Trp codon. These data provide the first direct evidence for post-translational bromination of a polypeptide which is translated through the normal cellular machinery. In addition to bromination, the peptide, which induces a "stiff tail" syndrome in mice, has several other modifications as shown by the sequence [Formula: See Text] in which Hyp = hydroxyproline. Asterisks indicate post-translational modifications (left to right): proteolytic cleavage at the N-terminus; hydroxylation of Pro3; epimerization of Trp4; bromination of Trp7, and C-terminal amidation. Bromocontryphan appears to have the highest density of post-translational modifications known among gene-encoded polypeptides. The overall result is a molecule which closely resembles marine natural products produced through specialized biosynthetic pathways comprising many enzyme-catalyzed steps.
Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D (2012)

Reciprocal mechanical interactions between cells and the extracellular matrix (ECM) are thought to play important instructive roles in branching morphogenesis. However, most studies to date have failed to characterize these interactions on a length scale relevant to cells, especially in three-dimensional (3D) matrices. Here we utilized two complementary methods, spatio-temporal image correlation spectroscopy (STICS) and laser optical tweezers-based active microrheology (AMR), to quantify endothelial cell (EC)-mediated deformations of individual ECM elements and the local ECM mechanical properties, respectively, during the process of capillary morphogenesis in a 3D cell culture model. In experiments in which the ECM density was systematically varied, STICS revealed that the rate at which ECs deformed individual ECM fibers on the microscale positively correlated with capillary sprouting on the macroscale. ECs expressing constitutively active V14-RhoA displaced individual matrix fibers at significantly faster rates and displayed enhanced capillary sprouting relative to wild-type cells, while those expressing dominant-negative N19-RhoA behaved in an opposite fashion. In parallel, AMR revealed a local stiffening of the ECM proximal to the tips of sprouting ECs. By quantifying the dynamic physical properties of the cell-ECM interface in both space and time, we identified a correlation linking ECM deformation rates and local ECM stiffening at the microscale with capillary morphogenesis at the macroscale.
Resource Management in Wireless Networks via Multi-Agent Deep Reinforcement Learning (2020)

We propose a mechanism for distributed radio resource management using multi-agent deep reinforcement learning to mitigate the interference among concurrent transmissions in wireless networks. We equip each transmitter in the network with a deep RL agent, which receives partial delayed observations from its own associated users, while also exchanging observations with its neighboring agents, and decides on which user to serve and what transmit power level to use at each scheduling interval. We propose a scalable agent design, where the dimensions of its observation and action spaces do not vary with changes in the environment configuration, e.g., in terms of number of transmitter and user nodes. Simulation results demonstrate the superiority of our proposed approach compared to decentralized baselines in terms of the tradeoff between average and 5 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> percentile user rates, while achieving performance close to, and even in certain cases outperforming, that of a centralized baseline.
Impact of nonpolar AlGaN quantum wells on deep ultraviolet laser diodes (2011)

The radiation properties of nonpolar AlGaN quantum wells (QWs) were theoretically investigated by comparing them to those of c-plane AlGaN QWs with heavy holes as the top valence band (VB). First, the conditions to minimize the threshold carrier density of c-plane QW laser diodes were explored. A thin well width (∼1 nm) and reduction of the Al content in the well layer were important to reduce threshold carrier density because narrow wells suppressed the quantum confined Stark effect and AlGaN with a lower Al content had a lower density of states. Moreover, the emission wavelength was widely controlled by tuning the Al contents of both the well and barrier layers under the proposed conditions. Then the properties of nonpolar AlGaN QWs were investigated. Nonpolar AlGaN had several superior characteristics compared to c-plane QWs, including large overlap integrals, optical polarization suitable for both edge and surface emissions, an almost linearly polarized optical dipole between the conduction band and top VB due to the isolated VBs, and a reduced VB density of state. Finally, the threshold carrier densities of both nonpolar and optimized c-plane QWs were compared as functions of the transition wavelength. At a given wavelength, the threshold of nonpolar QWs was lower than that of c-plane ones. Particularly below 260 nm, nonpolar QWs had a low threshold, whereas that of c-plane QWs drastically increased due to the large VB mass of AlN and carrier population in the crystal-field splitting band.
Fourier Domain Pump-Probe Optical Coherence Tomography imaging of Melanin (2009)

We report the first molecular image of melanin using a novel extension of OCT, pump-probe OCT. Melanin, an abundant endogenous chromophore, could provide general contrast in OCT imaging and means to diagnose and/or monitor melanomas.
SP-333, A Guanylate Cyclase C Agonist, Is A Safe and Well-Tolerated Locally Acting Drug Candidate for Treatment of Gastrointestinal Disorders and Diseases (2014)

Introduction: SP-333 is a proteolysis-resistant analog of uroguanylin, which is a physiological ligand of guanylate cyclase-C (GC-C). SP-333 activates GC-C expressed on epithelial cells lining the gastrointestinal (GI) mucosa stimulating cyclic GMP synthesis to regulate fluid transport, epithelial cell homeostasis and barrier function. Previously, we reported that oral treatment with SP-333 ameliorates GI inflammation in several murine models of colitis. We also reported that orally administered SP-333 promotes bowel movement in morphine or methadone induced constipation in rats. Objective of these phase I single ascending dose (SAD) and multiple ascending dose (MAD) clinical trials in healthy volunteers is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered SP-333. Methods: The SAD study included groups of 8 subjects each (6 active, 2 placebo) given a single oral dose of 0.1, 0.3, 1, 3, 10, 20, 30, or 60 mg of SP-333 tablets or placebo. The MAD study included 5 groups of 16 subjects each (12 active, 4 placebo) given a daily oral dose of 0.3, 1, 3, 10, or 30 mg of SP-333 tablets or placebo for 14 days. Treatment group 6 consisted of 8 subjects (6 active, 2 placebo) given a daily oral dose of 60 mg SP-333 or placebo for 7 days. Plasma PK samples were collected pre-dose and post-dose. PD assessments included time to first stool, stool frequency, and stool consistency using the Bristol stool form scale. All adverse events were documented. Results: Orally administered SP-333 was safe and tolerated at all dose levels. In the MAD study, SP-333 was safe up to 30 mg for 14 days and up to 60 mg for 7 days. All TEAEs resolved by completion of the study. The intolerable dose at 60 mg was identified because of two cases of fecal incontinence or soiling. This study was not powered to statistically assess the PD effect of orally administered SP-333, but the general trend in increased in BSFS scores, spontaneous bowel movement (SBM) frequency, and complete SBM (CSBM) frequency at doses higher than 1 mg is suggestive of the pharmacological action expected from an agent that activates GC-C to stimulate water secretion in the intestine. Conclusion: Orally administered SP-333, acting locally within the GI tract, was safe and well-tolerated. Maximum tolerated dose was declared at 30 mg. Data support further clinical development of SP-333. The drug is currently in clinical development for opioid-induced constipation and ulcerative colitis treatment. Disclosure - Kunwar Shailubhai, Laura Barrow, John Foss, Stephen Comiskey and Gary Jacob are employees of Synergy Pharmaceuticals, Inc.
Abstract 118: Methamphetamine Causes Endothelial Dysfunction Via Reduction Of Cystathionine Gamma Lyase And Hydrogen Sulfide Bioavailability (2021)

Background: Methamphetamine (METH) is an addictive illicit drug used worldwide that can elicit significant damage on blood vessels resulting in increased inflammation and cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left ventricular hypertrophy, and coronary artery disease in younger populations due to METH use making cardiovascular complications the second leading cause of death in METH substance users. The purpose of this study is to understand the underlying molecular mechanisms of METH-related cardiovascular injury. Methods and Results: Here we report that METH administration in a mouse model of ‘binge and crash’ decreases vascular function through a CSE/H 2 S/NO-dependent pathway. METH significantly reduced H 2 S and NO bioavailability in plasma and skeletal muscle tissues co-incident with a significant reduction in flow-mediated vasodilation (FMD) and blood flow velocity highlighting endothelial dysfunction. METH administration also reduced cardiac ejection fraction (EF) and fractional shortening (FS) indicating pump dysfunction. Interestingly, METH treatment selectively decreased CSE expression co-incident with reduced eNOS phosphorylation. Importantly, either exogenous H 2 S therapy or endothelial CSE transgenic overexpression corrected endothelial dysfunction and associated pathological responses due to METH toxicity. Conclusions: Our results uniquely demonstrate that METH mediates reduction of CSE expression and activity in endothelial cells, and subsequent attenuation of H 2 S/NO bioavailability directly leading to impaired cardiac and vascular function. Exogenous sulfide therapy or endothelial CSE transgenic overexpression rescues METH-induced vascular dysfunction.
Tolerogenic synthetic nanoparticles for the prevention of anti-drug antibodies against biologic therapies (TECH3P.936) (2015)

Abstract The development of anti-drug antibodies (ADAs) is a common cause for treatment failure and adverse events, such as hypersensitivity reactions, associated with biologic therapies. Therefore, prevention of ADAs in an antigen-specific manner would be highly desirable in order to improve the safety and efficacy of marketed products. Here we describe the use of SVP: polymeric, synthetic, biodegradable nanoparticles carrying a tolerogenic immunomodulator, rapamycin, to induce durable, antigen-specific immune tolerance. In mice, intravenous or subcutaneous co-injections of SVP with free antigen results in robust CD4+ T cell and B cell tolerance (i.e. the inhibition of their activation over multiple challenges), an increase in regulatory cells and the inhibition of antigen-specific hypersensitivity reactions. Only encapsulated rapamycin, not the free form, could induce immunological tolerance to a variety of antigens. Co-injections of SVP and antigen in both rats and cynomologous monkeys also results in B cell tolerance. In mice that spontaneously develop rheumatoid arthritis (RA), we show that treatment with SVP and adalimumab prevents the formation of anti-adalimumab ADAs therefore normalizing adalimumab pharmacokinetics and improving the clinical and histological manifestations of RA. SVP therapy represents a novel antigen-specific approach for the prevention of ADAs against biologic therapies, as well as the treatment of allergies and autoimmune diseases.
Recruitment of Factor H to the Streptococcus suis Cell Surface is Multifactorial (2016)

Streptococcus suis is an important bacterial swine pathogen and a zoonotic agent. Recently, two surface proteins of S. suis, Fhb and Fhbp, have been described for their capacity to bind factor H-a soluble complement regulatory protein that protects host cells from complement-mediated damages. Results obtained in this study showed an important role of host factor H in the adhesion of S. suis to epithelial and endothelial cells. Both Fhb and Fhbp play, to a certain extent, a role in such increased factor H-dependent adhesion. The capsular polysaccharide (CPS) of S. suis, independently of the presence of its sialic acid moiety, was also shown to be involved in the recruitment of factor H. However, a triple mutant lacking Fhb, Fhbp and CPS was still able to recruit factor H resulting in the degradation of C3b in the presence of factor I. In the presence of complement factors, the double mutant lacking Fhb and Fhbp was similarly phagocytosed by human macrophages and killed by pig blood when compared to the wild-type strain. In conclusion, this study suggests that recruitment of factor H to the S. suis cell surface is multifactorial and redundant.
QoS Aware Job Scheduling in a Cluster-Based Web Server for Multimedia Applications (2005)

We propose a cluster-based Web server where a few computing nodes are separately reserved for high-performance computing applications, such as multimedia, SSL, and CGI. As an example application, we consider a multimedia server that dynamically generates video units to satisfy the bit rate and bandwidth requirements of a variety of clients. To perform QoS aware scheduling of multiple multimedia jobs on the computing servers, a two-step algorithm is proposed. The first step is to fairly schedule multimedia streams to satisfy each stream's QoS requirement; and the second step is to balance the workload among heterogeneous computing nodes in the cluster. We propose a new quota-based adaptive coscheduling (QACS) algorithm that greatly reduces delay jitter by eliminating the out-of-order departure for outgoing streams, as well as achieves high throughput in a heterogeneous cluster. Experimental results show that the proposed scheduling technique gives adequate QoS guarantees to multiple streams.
Organic bistable memory characteristics with a photochromic diarylethene layer (2005)

Device structure dependence of the recording efficiency of organic bistable molecular memory using photochromic diarylethene (DAE) was studied. Devices with a thicker memory layer showed faster current decrease, that is, shorter writing time. This was attributed to effective isomerization at the many carrier traps in the memory layer. The device with an electron transport layer that consisted of a Silole derivative showed fast writing speed. The device with an Alq3 electron transport layer showed electroluminescence. This indicates the holes were transported through the DAE layer without contribution for isomerization. DAE molecules with good receptivity for both carriers should be developed for obtaining high speed memory.
Charging dynamics of single InAs quantum dots under both resonant and above-band excitation (2018)

We investigate the charging dynamics in epitaxially grown InAs quantum dots under resonant excitation with and without additional low-power above-band excitation. Time-resolved resonance fluorescence from a charged exciton (trion) transition is recorded as the above-band excitation is modulated on and off. The fluorescence intensity varies as the QD changes from charged to neutral and back due to the influence of the above-band excitation. We fit the transients of the time-resolved resonance fluorescence with models that represent the charging and neutralization processes. The time dependence of the transients indicate that Auger recombination of resonantly excited trions is largely responsible for neutralization of the charged state when the above-band excitation is off. The addition of above-band excitation revives the resonance fluorescence signal from the trion transition. We conclude that the above-band laser excites charges that relax into the bound state of the quantum dot via two different charge transport processes. The captured charges return the QD to its initial charge state and allow resonant excitation of the trion transition. The time dependence of one charge transport process is consistent with ballistic transport of charge carriers excited non-local to the QD via above-band excitation. We attribute the second charge transport process to carrier migration through a stochastic collection of weakly-binding sites, resulting in sub-diffusion-like dynamics.
Crystal structure of Hex1 reveals its mechanism of self-assembly and evolutionary origin (2002)

Biological macromolecular assemblies play significant roles in many biological reaction systems, including energy transfer, protein synthesis, protein analysis, DNA replication and signal transduction. More than 10,000 protein structures are now known since the first crystal structure of hemoglobin and myoglobin were determined. On the other hand, only a few macromolecule assembly structures including viruses have been determined by X-ray crystallography. This is because of the difficulties faced in the preparation, crystallization, Xray diffraction measurement, and crystal structure determination of large molecular assemblies. A beamline for biological macromolecular assemblies at SPring-8, which is specially designed to collect high resolution and high quality diffraction data of macromolecule assembly crystals with large unit cell, has been operating since September 1999. We have collected X-ray diffraction intensity data from some crystals of macromolecular assemblies. Diffraction data from a macromolecular assembly crystal with two unique axes of over 600 angstrom has been collected at 3.7 resolution. The present status of beamline and some diffraction data will be presented.
Pseudo-Color Encoding of Pictures by means of Halftone Screens and Coherent Optical Filtering (1976)

Pseudo-coloring of a photograph in a coherent optical processing system can be achieved through the utiliza-tion of the newly advanced technique of halftone screens. The basic principle of the pseudo-coloring method is to mix the high diffraction order outputs of the halftone photograph generated by lasers of different wave-lengths in a coherent optical system. A discussion of the theory, the method, and its potential applications will be given.© (1977) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Central Image Archiving and Management System for Multicenter Clinical Studies: Lessons from Low-dose CT for Appendicitis Trial (2017)

This special report aimed to document our experiences in implementing the Central Imaging Archiving and Management System (CIAMS) for a multicenter clinical trial, Low-dose CT for Appendicitis Trial (LOCAT), supported by the Korean Society of Radiology and Radiology Imaging Network of Korea for Clinical Research. LOCAT was a randomized controlled trial to determine whether low-dose CT is non-inferior to standard-dose CT with respect to the negative appendectomy rate in patients aged from 15 to 44 years. Site investigators downloaded the CT images from the site picture archiving and communication system servers, and uploaded the anonymized images to the primary server. CIAMS administrators inspected the images routed to the secondary server by a cross-check against image submission worksheets provided by the site investigators. The secondary server was automatically synchronized to the tertiary backup server. Up to June 2016, 2715 patients from 20 sites participated in LOCAT for 30 months. A total of 2539 patients' images (93.5%, 2539/2715) were uploaded to the primary server, 2193 patients' worksheets (80.8%, 2193/2715) were submitted, and 2163 patients' data (79.7%, 2163/2715) were finally monitored. No data error occurred.