gebhart/patrepeval huggingface dataset:
Pro-interleukin (IL)-1β Shares a Core Region of Stability as Compared with Mature IL-1β While Maintaining a Distinctly Different Configurational Landscape (2009)

Interleukin-1beta (IL-1beta) is a master cytokine involved in initiating the innate immune response in vertebrates (Dinarello, C. A. (1994) FASEB J. 8, 1314-1325). It is first synthesized as an inactive 269-residue precursor (pro-interleukin-1beta or pro-IL-1beta). Pro-IL-1beta requires processing by caspase-1 to generate the active, mature 153-residue cytokine. In this study, we combined hydrogen/deuterium exchange mass spectrometry, circular dichroism spectroscopy, and enzymatic digestion comparative studies to investigate the configurational landscape of pro-IL-1beta and the role the N terminus plays in modulating the landscape. We find that the N terminus keeps pro-IL-1beta in a protease-labile state while maintaining a core region of stability in the C-terminal region, the eventual mature protein. In mature IL-1beta, this highly protected region maps back to the area protected earliest in the NMR studies characterizing an on-route kinetic refolding intermediate. This protected region also encompasses two important functional loops that participate in the IL-1beta/receptor binding interface required for biological activity. We propose that the purpose of the N-terminal precursor region in pro-IL-1beta is to suppress the function of the eventual mature region while keeping a structurally and also functionally important core region primed for the final folding into the native, active state of the mature protein. The presence of the self-inhibiting precursor region provides yet another layer of regulation in the life cycle of this important cytokine.
Entrance Effects in a Two-Phase Slug Flow (1962)

This paper describes quantitatively one stage of the flow development process in equipment working with two-phase mixtures. The kinetics of a Taylor bubble, as it rises behind a series of other bubbles in a gas-liquid slug flow, have been determined. The rise velocity of a bubble is expressed as a function of separation distance from the bubble ahead of it. Using this information, the pattern of development of bubbles which initially enter a tube at regular intervals is determined by means of finite difference calculations. The density and, to a first approximation the pressure drop, of the developing flow are then calculated from continuity considerations. The density distribution in the entrance region is found to be a function of flow rates of the two phases, of distance from the inlet, and of initial bubble size. Density calculated by the present theory is compared with experimental measurements by the present and other investigators. Theory and experiments are in good agreement.
Critical Role of TrkB and Brain-Derived Neurotrophic Factor in the Differentiation and Survival of Retinal Pigment Epithelium (1997)

In the vertebrate eye, the retinal pigment epithelium (RPE) and the neural retina arise from a single layer of neuroectoderm. Factors influencing the differentiation of retinal neurons have been identified; however, little is known about molecules directing the differentiation of the RPE. Here we have found that the neurotrophin brain-derived neurotrophic factor (BDNF) plays an autocrine role in the differentiation and survival of Xenopus laevis RPE. Fluorescent in situ hybridization studies showed a precise co-expression of BDNF and its receptor trkB in the retinal neuroepithelium and actively differentiating RPE; in vitro studies demonstrated survival- and differentiation-promoting effects in serum-free explants and dissociated cultures. When a dominant negative mutant of the trkB receptor was expressed in developing embryos, severe arrest of RPE differentiation was seen with persistence of nestin- and Notch-positive neuroblasts.
Ocean Bottom Node Seismic at the Deepwater Bonga Field, Nigeria (2013)

Abstract The Bonga Main field, Nigeria's first deepwater discovery, was discovered by Shell Nigeria Exploration and Production Company (SNEPCo) in 1995 and is located approximately 120 km offshore at water depths of 800–1200m. First oil production started in November 2005, and Bonga has an average production capacity of 200,000 barrels/day. Oil production is from 4 main stacked turbidite reservoirs (690, 702, 710/740 and 803) using pressure maintenance via water injection through producer &amp; injector well pairs. The Bonga Main field is covered by an initial 1993 3D seismic streamer dataset and a block-wide exploration 2000 3D baseline seismic streamer survey. To monitor changes in reservoir dynamics since start of production in Q4 2005, a 4D seismic monitor streamer survey was acquired in Q1 2008. The Bonga 4D acquisition was completed on time, within budget, and with excellent HSE performance : the data quality was excellent (NRMS ~ 12.5%) where the (2000) baseline survey could be well repeated, but was of much poorer quality in the close vicinity to the field's surface obstructions (Floating Production, Storage and Off-loading vessel - FPSO and Surface Production Manifold - SPM). The 4D results of this survey added significant value to the development of the asset by improving the understanding of reservoir connectivity and the sweep efficiency between injector and producer wells, making the project a clear technical and business success. Figure 1 shows the amplitude maps of the 702 reservoir for the 2000 baseline, 2008 monitor, and the 4D difference. The bright colors indicate the presence of oil, with the 4D difference map clearly showing where water has replaced oil.
Fiber-laser-based photoacoustic microscopy and melanoma cell detection (2011)

For broad applications in biomedical research involving functional dynamics and clinical studies, a photoacoustic microscopy system should be compact, stable, and fast. In this work, we use a fiber laser as the photoacoustic irradiation source to meet these goals. The laser system measures 45×56×13 cm3. The stability of the laser is attributed to the intrinsic optical fiber-based light amplification and output coupling. Its 50-kHz pulse repetition rate enables fast scanning or extensive signal averaging. At the laser wavelength of 1064 nm, the photoacoustic microscope still has enough sensitivity to image small blood vessels while providing high optical absorption contrast between melanin and hemoglobin. Label-free melanoma cells in flowing bovine blood are imaged in vitro, yielding measurements of both cell size and flow speed.
Efficacy of a fixed combination of 0.09 % xanthan gum/0.1 % chondroitin sulfate preservative free vs polyethylene glycol/propylene glycol in subjects with dry eye disease: a multicenter randomized controlled trial (2016)

ClinicalTrials.gov: NCT01657253 . Date of registration May 19, 2014.
On the role of the C-terminus of α-calcitonin-gene-related peptide (αCGRP). The structure of des-phenylalaninamide37-αCGRP and its interaction with the CGRP receptor (1993)

alpha-Calcitonin-gene-related peptide (alpha CGRP) lacking its C-terminal phenylalaninamide residue was found not to bind to its receptor as did full-length (amidated) alpha CGRP. Investigation of the structure of these peptides by c.d. and n.m.r. revealed no significant difference, so it seemed that the effect of deleting the C-terminal phenylalaninamide on the biological activity of alpha CGRP was not by disruption of the peptide's structure. Thus the C-terminal phenylalaninamide is an important factor in this ligand-receptor interaction, and the group itself may interact directly with the receptor.
CAR T cells: driving the road from the laboratory to the clinic (2013)

Summary Blockbuster antibody therapies have catapulted immune‐based approaches to treat cancer into the consciousness of mainstay clinical research. On the back of this, other emerging immune‐based therapies are providing great promise. T‐cell therapy is one such area where recent trials using T cells genetically modified to express an antibody‐based chimeric antigen receptor ( CAR ) targeted against the CD 19 antigen have demonstrated impressive responses when adoptively transferred to patients with advanced chronic lymphocytic leukemia. The general concept of the CAR T cell was devised some 20 years ago. In this relatively short period of time, the technology to redirect T‐cell function has moved at pace facilitating clinical translation; however, many questions remain with respect to developing the approach to improve CAR T‐cell therapeutic activity and also to broaden the range of tumors that can be effectively targeted by this approach. This review highlights some of the underlying principles and compromises of CAR T‐cell technology using the CD 19‐targeted CAR as a paradigm and discusses some of the issues that relate to targeting solid tumors with CAR T cells.
Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification (1999)

BACKGROUND Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of disease chronicity. However, there is a serious lack of agreement about how to describe and classify the appearance of reflux oesophagitis AIMS To examine the reliability of criteria that describe the circumferential extent of mucosal breaks and to evaluate the functional and clinical correlates of patients with reflux disease whose oesophagitis was graded according to the Los Angeles system. METHODS Forty six endoscopists from different countries used a detailed worksheet to evaluate endoscopic video recordings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clinical trials of omeprazole treatment (277 patients). RESULTS Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended between the tops of mucosal folds, gave acceptable agreement (mean κ value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0–25%, 26–50%, 51–75%, 76–99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean κ values 0–0.15) for all but the lowest category of extent (mean κ value 0.4). Severity of oesophageal acid exposure was significantly (p&lt;0.001) related to the severity grade of oesophagitis. Preteatment oesophagitis grades A–C were related to heartburn severity (p&lt;0.01), outcomes of omeprazole (10 mg daily) treatment (p&lt;0.01), and the risk for symptom relapse off therapy over six months (p&lt;0.05). CONCLUSIONS Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis.
Rapid detection of single bacteria in unprocessed blood using Integrated Comprehensive Droplet Digital Detection (2014)

Blood stream infection or sepsis is a major health problem worldwide, with extremely high mortality, which is partly due to the inability to rapidly detect and identify bacteria in the early stages of infection. Here we present a new technology termed 'Integrated Comprehensive Droplet Digital Detection' (IC 3D) that can selectively detect bacteria directly from milliliters of diluted blood at single-cell sensitivity in a one-step, culture- and amplification-free process within 1.5-4 h. The IC 3D integrates real-time, DNAzyme-based sensors, droplet microencapsulation and a high-throughput 3D particle counter system. Using Escherichia coli as a target, we demonstrate that the IC 3D can provide absolute quantification of both stock and clinical isolates of E. coli in spiked blood within a broad range of extremely low concentration from 1 to 10,000 bacteria per ml with exceptional robustness and limit of detection in the single digit regime.
PLoS Biology in Action (2004)

Some examples of how the PLoS Biology content is used and a request for feedback from creative users
Effect of the conformation of a peptide from gp41 on binding and domain formation in model membranes (1995)

Binding of the peptide fragment 828-848 (P828), amino acid sequence RVIEVVQGACRAIRHIPRRIR, from the carboxy-terminal region of the envelope glycoprotein gp41 of human immunodeficiency virus type 1 (HIV-1) to membranes composed of a mixture of neutral and negatively charged phospholipids results in domain or cluster formation of the charged lipid. The conformation and dynamics of the peptide are investigated in solution and in the presence of sodium dodecyl sulphate (SDS) micelles using high resolution nuclear magnetic resonance (NMR) spectroscopy and circular dichroism (CD) spectropolarimetry. The CD results demonstrate that addition of either SDS, negatively charged phospholipid liposomes, or trifluoroethanol (TFE) induces a conformational transition of the peptide from a random coil or an extended chain in water to a more ordered structure with an estimated helical content of up to 60%. The structure of the peptide in a membrane mimetic SDS solution was investigated in detail using two-dimensional NMR. The measurements demonstrate the existence of a helical component in the peptide conformation in the SDS-bound state. The peptide most likely exists as an ensemble of conformations with exchange times between them which are fast on the chemical shift NMR time scale (10(-3) s). Simple neutralization of the six arginine sidechain charges does not cause the peptide to adopt an ordered structure. Thus, there is an additional requirement for the structural transition such as that resulting from constraint of the peptide on a surface, or localization of the peptide at the lipid-water interface where the polarity is lower.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium-independent cell volume regulation in human lymphocytes. Inhibition by charybdotoxin. (1990)

The properties of the K+ pathway underlying regulatory volume decrease (RVD) in human blood lymphocytes were investigated. Evidence is presented for the existence of three types of K+ conductance in these cells. Ionomycin, a Ca2+ ionophore, induced a K(+)-dependent hyperpolarization, indicating the presence of Ca2(+)-activated K+ channels, which were blocked by charybdotoxin (CTX). CTX also induced a depolarization of the resting membrane potential, even at subphysiological cytosolic [Ca2+]([Ca2+]i), which suggests the existence of a second CTX-sensitive, but Ca2(+)-independent conductance. A CTX-resistant K+ conductance was also detected. RVD in blood lymphocytes was partially (approximately 75%) blocked by CTX. However, volume regulation was not accompanied by detectable changes in [Ca2+]i, nor was it prevented by removal of extracellular Ca2+ and depletion or buffering of intracellular Ca2+. These observations suggest that K+ loss during RVD is mediated by Ca2(+)-independent, CTX-sensitive channels or that Ca2(+)-dependent channels can be activated by cell swelling at normal or subnormal [Ca2+]i. The former interpretation is supported by findings in rat thymic lymphocytes. These cells also displayed a CTX-sensitive Ca2(+)-dependent hyperpolarization. However, CTX did not significantly alter the resting potential, suggesting the absence of functional Ca2(+)-independent, toxin-sensitive channels. Volume regulation in thymic lymphocytes was less efficient than in human blood cells. In contrast to blood lymphocytes, RVD in thymocytes was not affected by CTX. These observations indicate that, though present in lymphocytes, Ca2(+)-activated K+ channels do not play an important role in volume regulation. Instead, RVD seems to be mediated by Ca2(+)-independent K+ channels. We propose that two types of channels, one CTX sensitive and the other CTX insensitive, mediate RVD in human blood lymphocytes, whereas only the latter type is involved in rat thymocytes.
CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand (1998)

grantor: University of Toronto
Novel transmission lines for the submillimeter-wave region (1992)

A detailed presentation of the available information on the electrical properties of submillimeter-wave transmission lines is given. These lines are compared with conventional planar and nonplanar lines, such as microstrip and rectangular waveguide, in terms of performance, fabrication feasibility, and availability. Four types of novel monolithic waveguides that have shown promise for use in the submillimeter frequency range are examined. The advantages and disadvantages associated with the use of these guides are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A rapid admission protocol to reduce emergency department boarding times (2010)

Institution of a rapid admission protocol successfully reduced overall EDBT at our institution, although few gains were noted for patients with a telemetry or ICU destination. In total, the intervention saved 27 884 h, or 1161 emergency department patient-days, over the course of a single year.
22 SV40 and Polyomavirus DNA Replication (1996)

The papovavirus family comprises two virus subgroups: the polyomaviruses and the papillomaviruses. The polyomavirus subgroup consists of a dozen members and includes simian virus 40 (SV40), the murine polyomavirus (PyV), and two human isolates, JCV and BKV (for review, see Tooze 1980). The polyomaviruses display strict species specificity for their replication, but otherwise share a common architecture, genome organization, and replication cycle. SV40 replicates in simian cells and to a lesser extent in human cells, whereas PyV replicates in cells of murine origin. The circular double-stranded DNA genomes of SV40 and PyV comprise about 5300 bp. The viral DNA is assembled into chromatin both in virions and in infected cells, and apart from the absence of histone H1, it is structurally indistinguishable from that of the cell. This review focuses principally on the replication of SV40 DNA and draws on the PyV literature to highlight differences between these two papovaviruses where appropriate. Several excellent reviews on this subject have appeared recently (DePamphilis and Bradley 1986; Challberg and Kelly 1989; Stillman 1989; Hurwitz et al. 1990; Melendy and Stillman 1992). We refer the reader to these and to other chapters in this volume for more in-depth discussion of topics we are unable to describe here and for more comprehensive citations to the primary literature. Since their discovery in the late 1950s, SV40 and PyV have served as paradigms to understand cellular processes as diverse as DNA replication, transcription, and oncogenic transformation. The rationale for employing these viruses as models for DNA...
Substrate-specific Activation of Sirtuins by Resveratrol (2005)

Resveratrol, a small molecule found in red wine, is reported to slow aging in simple eukaryotes and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to act as a sirtuin activator, and this property has been proposed to account for its anti-aging effects. We show here that resveratrol is a substrate-specific activator of yeast Sir2 and human SirT1. In particular, we observed that, in vitro, resveratrol enhances binding and deacetylation of peptide substrates that contain Fluor de Lys, a non-physiological fluorescent moiety, but has no effect on binding and deacetylation of acetylated peptides lacking the fluorophore. Consistent with these biochemical data we found that in three different yeast strain backgrounds, resveratrol has no detectable effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and life span. In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined.
CO2 homeostasis during periodic breathing: predictions from a computer model (1993)

The Bohr/Riley model of CO2 homeostasis describes the relationship between CO2 production, ventilation, and arterial PCO2 and assumes that ventilation and CO2 delivery to the lung are both anatomically and temporally well matched. In contrast to normal breathing, periodic patterns of ventilation show temporal mismatch of ventilation to CO2 delivery. We developed a computer model of lung CO2 clearance that uses CO2 transfer equations to generate iterative solutions for PCO2 in multiple body compartments as a function of time. During continuous ventilatory patterns our model predicts steady-state arterial PCO2 identical to that of the Bohr model. During periodic ventilation, we predict mean PCO2 will be elevated unless mean ventilation is increased above that required by the Bohr model. Waxing and waning tidal volumes, low functional residual capacity, and low capillary blood volume potentiate the hypercapnia. However, if cardiac output oscillates in phase with breathing, hypercapnia is minimized. This analysis suggests a new mechanism for the development of sustained hypercapnia, separate from absolute hypoventilation or the presence of lung disease.
Activation, orientation and landing of female Culex quinquefasciatus in response to carbon dioxide and odour from human feet: 3‐D flight analysis in a wind tunnel (2010)

This study investigated the interaction between carbon dioxide (CO(2) ) and human foot odour on activation, upwind orientation and landing of host-seeking female Culex quinquefasciatus (Say) (Diptera: Culicidae) in a wind tunnel. More mosquitoes landed on warmed glass beads coated with foot odour than on clean beads; adding a plume of 4% CO(2) did not influence the proportion of mosquitoes landing. A second experiment used 3-dimensional video tracking to assess flight performance. Activation was more rapid with CO(2) and with CO(2) + foot odour than with clean air or with foot odour alone. Upwind flights were fastest with CO(2) and with clean air, and slowest with foot odour; the CO(2) + foot odour treatment overlapped the previous three treatments in significance. Flight headings tended more towards due upwind with CO(2) and with clean air than with CO(2) + foot odour or with foot odour alone. In both experiments, many mosquitoes flew upwind in clean air. There was little evidence of females changing course upon entering or exiting the CO(2) plume or reacting to foot odour during flight.
Percutaneous Epicardial Left Atrial Appendage Closure: Preliminary Results of an Electrogram Guided Approach (2009)

Using electrical navigation, percutaneous epicardial LAA ligation with a remotely tightened suture was performed successfully within the confines of the intact pericardial space. This technique may allow decreasing the risk of stroke in AF patients without the need for thoracotomy or an endocardially placed prosthetic device.
Hyperbolic metamaterials based on quantum-dot plasmon-resonator nanocomposites (2014)

We theoretically demonstrate that nanocomposites made of colloidal semiconductor quantum dot monolayers placed between metal nanoparticle monolayers can function as multilayer hyperbolic metamaterials. Depending on the thickness of the spacer between the quantum dot and nanoparticle layers, the effective permittivity tensor of the nanocomposite is shown to become indefinite, resulting in increased photonic density of states and strong enhancement of quantum dot luminescence. This explains the results of recent experiments [T. Ozel et al., ACS Nano 5, 1328 (2011)] and confirms that hyperbolic metamaterials are capable of increasing the radiative decay rate of emission centers inside them. The proposed theoretical framework can also be used to design quantum-dot/nanoplasmonic composites with optimized luminescence enhancement.