gebhart/patrepeval huggingface dataset:
278. Successful Correction of Rag1 Severe Combined Immunedefciency at Clinically Relevant Vector Copy Numbers (2015)

RAG1 -SCID patients lack B- and T lymphocytes due to the inability to rearrange immunoglobulin (Ig) and T-cell receptor (TCR) genes. Gene therapy is a valid treatment alternative for RAG1-SCID patients lacking an appropriate bone marrow donor. However, developing such therapy for RAG1 has proven difficult. As proof-of-principle, we have previously shown with an SFFV promoter element that sufficient RAG1 expression could be achieved for correction at clinically acceptable vector copy numbers (VCN). In our current study, we tested clinically relevant lentiviral SIN vectors with different internal promoter elements (UCOE, PGK, MND, and UCOE-MND in tandem) to deliver human RAG1 sequences. In vitro assessment of promoter strength was done on transduced mouse lineage-depleted cells. The highest RAG1 expression per VCN was reached with the MND and the UCOE-MND containing vectors, followed by UCOE. The PGK displayed the lowest promoter strength, 3 to 10 times weaker than the other elements. Next, we used Rag1-/- mice as a preclinical model for RAG-SCID to assess the capacity of the various vectors to correct the SCID phenotype at very low to moderate VCN (0.01-0.2), where the VCN positively correlating with the RAG1 expression levels. All gene therapy-treated mice reconstituted their peripheral T cell compartment, however in animals that received a transplant with low RAG1 expression (n=9) this effect was limited to peripheral blood. When assessing phenotypic data from thymus 17 weeks after transplantation, only mice that received a transplant with high RAG1 expression, showed a thymocyte subset composition comparable to mice receiving wild type cells. This included a high percentage and number of double positive (DP) cells, assuring an ongoing supply of peripheral T cells. Mice receiving a transplant with low RAG1 expression levels, were mostly lacking the DP population. Similarly, when looking at developing B cells in the bone marrow, animals that were transplanted with cells with low RAG1 expression did not have a substantial number of surface IgM+ cells. This in contrast to animals that received cells with high RAG1 expression levels in which developing B cell subsets were readily detectable. These findings were paralleled in the peripheral blood, where the fraction of B220+ cells positively correlated with RAG1 expression in the transplant material. In the low RAG1 expression groups, we found that a number of mice developed skin rashes, while animals in the high RAG1 expression group as well as animals that received wild type cells or uncorrected Rag1-/- cells did not display any health problems. We are currently determining the TCR repertoire, since a limited repertoire could point to autoreactive T cells causing the rashes. To conclude, the level of B- and T cell development in primary lymphoid organs is directly correlated to the RAG1 expression levels in the transplant and we were able to obtain sufficient RAG1 expression for full T and B cell reconstitution even at a moderate, but clinically relevant, VCN.
Ultrastructural Anatomy of Contracted Capsules Around Textured Implants in Augmented Breasts (2001)

The development of a capsule around an implant is part of the physiological response to a foreign body. Capsular contracture is the most specific and frustrating complication of augmentation mammaplasty, and a lot of studies have been devoted to it. The aim of the current study is to examine the fine architecture of the contracted capsule around textured implants in humans. Eight capsules from augmented and contracted breasts with gel-filled, textured-surface silicone implants were studied after standard preparation for light and scanning electron microscopy, and after partial digestion in sodium hydroxide. Two capsules from contracted breasts around smooth implants and two noncontracted capsules around textured implants were prepared and studied in the same fashion as controls. A multilayer structure of the contracted capsule was seen, and the architecture of the various layers is described. The inner surface presents irregular craterlike depressions. The arrangement of collagen fibers varies in capsule layers. The effect of a textured-surface implant on the mechanism of capsule contraction based on the observed capsular architecture is that only part of the capsule is effective mechanically in producing a contracting force. A thin vascular layer was identified near the inner surface in contracted capsules around textured implants, and the authors' think that this layer is probably the key structure in the histological development and growth of the capsule.
Organophosphorus Flame Retardants and Plasticizers in Swedish Sewage Treatment Plants (2005)

The levels, distribution, and possible sources of 12 organophosphorus flame retardants and plasticizers, some of which are reported to be toxic to aquatic organisms, were investigated in samples of influents, effluents, and sludge from 11 Swedish sewage treatment plants (STPs). The organophosphorus compounds (OPs) studied were poorly removed from the wastewater; especially the chlorinated OPs tended to pass through the STPs without being removed or degraded, while alkyl-OPs, such as tributyl phosphate (TBP), were more successfully removed. In both influents and effluents, tris(2-butoxyethyl) phosphate and TBP were the most prominent substances followed by tris(2-chloroisopropyl) phosphate (TCPP). The highest concentration of any individual OP detected in the influents was 52 microg L(-1) (TBP). Ethylhexyl diphenyl phosphate and TCPP dominated in all sludge samples. A budget calculation comparing the annual amount of OPs in the influent received by Swedish STPs with the known amount of OPs imported indicated that approximately 15% is emitted to STPs. Of the total amount of OPs reaching the STPs annually, 49% is degraded, 50% (27 tons) is emitted to the recipients, and only 1% ends up in the sludge. The concentrations of most OPs were quite similar among the sampled STPs, indicating that the data may be applicable in other STPs.
Effects of heparin on liver fibrosis in patients with chronic hepatitis B (2003)

Heparin/LMWH can inhibit collagen proliferation in liver tissues with hepatitis B.
Noninvasive Sialic Acid Detection at Cell Membrane by Using Phenylboronic Acid Modified Self-Assembled Monolayer Gold Electrode (2009)

Alternations of sialic acid (SA) content on cell surface glycan chains have been implicated in numerous normal and pathological processes including developments, differentiations, and tumor metastasis. Overexpressions of SA have been implicated in the malignant and metastatic phenotypes for many different types of cancers, while decreased SA expression has also been identified in erythrocytes of diabetic mellitus. Techniques to conveniently monitor cell surface SA would therefore have great relevance to cytology. Preexisting methodologies to quantify SA, however, involve multiple enzymatic, dye-labeling, and lethal procedures, which are costly and time-consuming. Here we developed a potentiometric SA detection using a phenylboronic acid (PBA) compound integrated into the form of a self-assembled monolayer (SAM) onto a field effect transistor (FET) extended gold gate electrode. Due to selective binding between undisassociated PBA and SA at pH 7.4 among other glycan chain constituent monosaccharides, we found that carboxyl anions of SA were exclusively detectable as the change in threshold voltage (V(T)) of the PBA-modified FET. The technique was applied to analyses of altered SA expressions on rabbit erythrocyte as a model for diabetes. Comparative SA expression analyses for each healthy and diseased model revealed that the disease could be feasibly diagnosed simply by placing the known-count cell suspensions onto the device without any labeling and enzymatic procedures. Such a technique may also provide a quantitative adjunct to histological evaluation of tumor malignancy and metastatic potential during intra- and postoperative diagnoses. Also advantageously, a technique herein described is all within a CMOS (Complementary Metal Oxide Semiconductor) compatible format thus promising for highly efficient and low cost manufacturing with readiness of downsizing and integration by virtue of advanced semiconductor processing technologies.
Neural control in vergence eye movements (2010)

Vergence eye movements are the inward and outward turning of the eyes and contemporary views believe these movements are mediated by a preprogramming and feedback controlled mechanism. The individual left and right eye responses have been reported to have large dynamic asymmetries between the individual eye movements. One hypothesis to explain the observed asymmetry is the preprogrammed transient component is monocularly controlled. A visual stimulus was created to stimulate a single step change to one eye and a double step change to the other eye using a haploscope. Results show that in some responses a double high-velocity component was observed in one response with a single high-velocity response in the other eye. This behavior suggests the preprogrammed component within a vergence response may be monocularly controlled.
Feedback control of electrical stimulation electrode arrays (2016)

Electrical stimulation electrode arrays are an emerging technology that enables muscles to be artificially contracted through the activation of their associated motor neurons. A principal application of electrical stimulation is to assist human motion for orthotic or therapeutic purposes. This paper develops a framework for the design of model-based electrode array feedback controllers that balance joint angle tracking performance with the degree of disturbance and modeling mismatch that can exist in the true underlying biomechanical system. This framework is used to develop a simplified control design procedure that is suitable for application in a clinical setting. Experimental results evaluate the feasibility of the control design approach through tests on ten participants using both fabric and polycarbonate electrode arrays.
Maternal omega‐3 fatty acid consumption decreases offspring reactivity to the stress of a novel environment (684.3) (2014)

Prenatal supplementation with omega‐3 fatty acids (O3FAs) is common because O3FAs are integral to fetal brain development. Our objective was to assess effects of prenatal O3FA consumption on offspring behavior using a rat model. Pups were obtained from the second litter of mothers that consumed diets with or without O3FAs for two cycles of gestation and lactation. The without‐O3FA diet contained 7% sunflower oil, which depletes maternal brain O3FA levels. The with‐O3FA diet contained 7% menhaden oil (26% O3FAs). Pups were weaned at age 21 days to the facility chow diet, which contained 0.2 g O3FA/100 g. Behavioral testing began at 8 weeks of age. The offspring were tested in the open field (OF) to examine locomotor reactivity to the stress of being placed in a novel environment, the holeboard task (HBT) to assess memory, and the forced swim test (FST) to assess depression‐related behavior. Offspring from O3FA‐consuming mothers were less reactive to novel OF stress than pups from O3FA‐deficient mothers, F(1,16) = 9.613, p = 0.007. In the HBT, offspring whose mothers ate O3FAs tended to have improved working memory, F(1,15) = 3.03, p = 0.10, but more subjects are needed for statistical power. Maternal O3FA intake did not influence offspring immobility in the FST. Taken together, these data indicate that maternal consumption of O3FAs during gestation and lactation may dampen stress reactivity and improve the memory of offspring. Grant Funding Source : Research Enhancement Program of Texas State University
Faster History Matching and Uncertainty in Predicted Production Profiles With Stochastic Modeling (1993)

Abstract High resolution sequence stratigraphical methods have been used in the detailed geological modeling of an element of the Ness formation of a North Sea field. This updated geological description has been used as input to the stochastic geological model MOHERES. 14 realizations of facies architecture and petrophysical properties have been generated. The stochastically generated realizations have been scaled up to a refined element of an existing deterministic, history matched reservoir simulation model for the full Upper Brent reservoir. The upscaled versions of the realizations have been connected to the full field model, and reservoir simulations have been performed to compare twelve years of production history with simulated results for well production, RFT- and PLT-data. Six of the realizations gave good to very good results when compared to measured production data. These realizations were used for simulation of the future production performance to the year 2010, making it possible to estimate its uncertainty.
Online smooth trajectory planning for mobile robots by means of nonlinear filters (2010)

The paper presents a nonlinear filtering technique that can be adopted to generate smooth trajectories for mobile robotic applications. The proposed trajectory planner can be fully executed online by the robot control system, thanks to its inherently discrete-time behavior and to its limited computational requirement. The outputs of the nonlinear filter used as a trajectory planner include the derivatives of the desired position in the cartesian plane up to the third order. This allows the implementation of feedback linearization control schemes that can transform the dynamics of a mobile robot in a double chain of three integrators, exploiting the highest derivative of the filter's output as a feedforward action. Finally, the paper reports experimental results obtained by the full implementation of the proposed trajectory planning and control scheme on a real unicycle-like robot.
Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression (2017)

Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.
Parametric Study of Fluidic Oscillators for Use in Active Boundary Layer Control (2011)

A parametric study was conducted to identify the main factors influencing the frequency produced by fluidic oscillators with the goal of using the actuator to trigger boundary layer transition through the excitation of Tollmien Schlichting waves. Test bench conditions were chosen to match the static pressure at the actuation position on the candidate blade profile for a cascade exit Mach number of 0.6 and Reynolds numbers from 60,000 to 200,000. The inlet vs. outlet pressure ratio and the position and geometry of the outlet holes were all varied. Additionally, the effect of the oscillator’s scale and the feedback channel geometry were considered. The flow at the exit was measured using a hot wire, while Kulite pressure transducers were used to measure pressure fluctuations within the device. This paper shows that fluidic oscillators can achieve frequencies of 10 kHz and that the parameters considered play an important role in the performance of these devices.
Neuromodulation Techniques for Medically Refractory Chronic Pain (1993)

Advances in our knowledge of the physiology of pain transmission and modulation have created new surgical options for the control of chronic pain. The pain modulation network can be activated by administration of spinal opiates or by electrical stimulation of the nervous system with transcutaneous, peripheral nerve, spinal cord, and deep brain stimulation. The theoretical basis and the clinical applications of neurostimulation for the treatment of medically intractable chronic pain are reviewed.
Human uterine cervical epithelial cells grown on permeable support – a new model for the study of differentiation (1994)

The purpose of the present study was to establish culture conditions for human uterine cervical epithelial cells on permeable support and to determine how it affects cervical cell differentiation. Human ectocervical epithelial cells (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on collagen-coated filters. Culture conditions, density of cells in culture and expression of epithelial and cervical-cell phenotypic markers were determined and compared in cells grown on filter and on solid support. Compared with the latter, cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell layers compared to 1-3 on solid support, and cells of all three types expressed intercellular tight junctions. The cytokeratin profiles revealed differences between the three cell types as well as differences within the same cell species when grown on filter, compared to solid support. Of particular importance was the finding of a higher expression of K-13 in hECE grown on filter compared to solid support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE and ECE16-1 expressed involucrin protein, the level of which in both was higher in cells grown on filter compared to solid support. Polarization of the cultures was determined by morphology (stratification of hECE cells, expression of pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc) under voltage-clamp conditions. Confluency of the cultures was determined by measuring transepithelial unidirectional fluxes of inert molecules with different molecular weights (MWs) through the paracellular pathway, and by measuring transepithelial conductance. The results indicated transepithelial permeability of 7-22.10(-6) cm.sec-1, which was 5-100 fold smaller compared to blank inserts, with a cut-off MW of 40-70 kDa for hECE and Caski cells. Transepithelial conductance ranged 18.5 to 51.5 mS.cm-2, indicating a leaky but confluent epithelia. Collectively the results indicate the epithelial nature of the cells and their improved differentiation when grown on filter support; hECE is a model for ectocervical epithelium while ECE16-1 and Caski express phenotypic characteristics of squamous metaplastic cervical epithelium and endocervical epithelium respectively.
Coated dielectric-slab beam splitter for a polarization-independent Michelson interferometer (1986)

A high-index dielectric slab can be coated on one face with a low-index thin film of quarterwave optical thickness at oblique incidence so that it reflects monochromatic light as a halfwave retarder and refracts it without change of polarization. The other (exit) face of the slab is coated with a bilayer that produces total refraction of light also without change of polarization. When this coated slab is used as a beam splitter (BS) in a Michelson interferometer, it renders its operation completely independent of source polarization. A specific example is presented of a coated Ge-slab BS for 10.6- μ m radiation and 45° angle of incidence. Such a BS is tolerant to film-thickness errors and is reasonably achromatic over a small (10–11- μ m) wavelength range.
Genome-wide patterns of genetic diversity, population structure and demographic history in mānuka (Leptospermum scoparium) growing on indigenous Māori land (2021)

Leptospermum scoparium J. R. Forst et G. Forst, known as mānuka by Māori, the indigenous people of Aotearoa (New Zealand), is a culturally and economically significant shrub species, native to New Zealand and Australia. Chemical, morphological and phylogenetic studies have indicated geographical variation of mānuka across its range in New Zealand, and genetic differentiation between New Zealand and Australia. We used pooled whole genome re-sequencing of 76 L. scoparium and outgroup populations from New Zealand and Australia to compile a dataset totalling ~2.5 million SNPs. We explored the genetic structure and relatedness of L. scoparium across New Zealand, and between populations in New Zealand and Australia, as well as the complex demographic history of this species. Our population genomic investigation suggests there are five geographically distinct mānuka gene pools within New Zealand, with evidence of gene flow occurring between these pools. Demographic modelling suggests three of these gene pools have undergone expansion events, whilst the evolutionary histories of the remaining two have been subjected to contractions. Furthermore, mānuka populations in New Zealand are genetically distinct from populations in Australia, with coalescent modelling suggesting these two clades diverged ~9 –12 million years ago. We discuss the evolutionary history of this species and the benefits of using pool-seq for such studies. Our research will support the management and conservation of mānuka by landowners, particularly Māori, and the development of a provenance story for the branding of mānuka based products.
Energy penetration into arrays of aligned nanowires irradiated with relativistic intensities: Scaling to terabar pressures (2017)

Ultrahigh-energy density (UHED) matter, characterized by energy densities >1 × 10<sup>8</sup> J cm<sup>-3</sup> and pressures greater than a gigabar, is encountered in the center of stars and inertial confinement fusion capsules driven by the world's largest lasers. Similar conditions can be obtained with compact, ultrahigh contrast, femtosecond lasers focused to relativistic intensities onto targets composed of aligned nanowire arrays. We report the measurement of the key physical process in determining the energy density deposited in high-aspect-ratio nanowire array plasmas: the energy penetration. By monitoring the x-ray emission from buried Co tracer segments in Ni nanowire arrays irradiated at an intensity of 4 × 10<sup>19</sup> W cm<sup>-2</sup>, we demonstrate energy penetration depths of several micrometers, leading to UHED plasmas of that size. Relativistic three-dimensional particle-in-cell simulations, validated by these measurements, predict that irradiation of nanostructures at intensities of >1 × 10<sup>22</sup> W cm<sup>-2</sup> will lead to a virtually unexplored extreme UHED plasma regime characterized by energy densities in excess of 8 × 10<sup>10</sup> J cm<sup>-3</sup>, equivalent to a pressure of 0.35 Tbar.