gebhart/patrepeval huggingface dataset:
Aberrant Splicing in Transgenes Containing Introns, Exons, and V5 Epitopes: Lessons from Developing an FSHD Mouse Model Expressing a D4Z4 Repeat with Flanking Genomic Sequences (2015)

The DUX4 gene, encoded within D4Z4 repeats on human chromosome 4q35, has recently emerged as a key factor in the pathogenic mechanisms underlying Facioscapulohumeral muscular dystrophy (FSHD). This recognition prompted development of animal models expressing the DUX4 open reading frame (ORF) alone or embedded within D4Z4 repeats. In the first published model, we used adeno-associated viral vectors (AAV) and strong viral control elements (CMV promoter, SV40 poly A) to demonstrate that the DUX4 cDNA caused dose-dependent toxicity in mouse muscles. As a follow-up, we designed a second generation of DUX4-expressing AAV vectors to more faithfully genocopy the FSHD-permissive D4Z4 repeat region located at 4q35. This new vector (called AAV.D4Z4.V5.pLAM) contained the D4Z4/DUX4 promoter region, a V5 epitope-tagged DUX4 ORF, and the natural 3' untranslated region (pLAM) harboring two small introns, DUX4 exons 2 and 3, and the non-canonical poly A signal required for stabilizing DUX4 mRNA in FSHD. AAV.D4Z4.V5.pLAM failed to recapitulate the robust pathology of our first generation vectors following delivery to mouse muscle. We found that the DUX4.V5 junction sequence created an unexpected splice donor in the pre-mRNA that was preferentially utilized to remove the V5 coding sequence and DUX4 stop codon, yielding non-functional DUX4 protein with 55 additional residues on its carboxyl-terminus. Importantly, we further found that aberrant splicing could occur in any expression construct containing a functional splice acceptor and sequences resembling minimal splice donors. Our findings represent an interesting case study with respect to AAV.D4Z4.V5.pLAM, but more broadly serve as a note of caution for designing constructs containing V5 epitope tags and/or transgenes with downstream introns and exons.
Species-specific diversity among simian immunodeficiency viruses from African green monkeys (1991)

The prevalence, natural history, and genetic characteristics of simian immunodeficiency virus (SIV) infections in most feral African monkey species are presently unknown, yet this information is essential to elucidate their origin and relationship to other simian and human immunodeficiency viruses. In this study, a combination of classical and molecular approaches were used to identify and characterize SIV isolates from West African green monkeys (Cercopithecus sabaeus) (SIVagm isolates). Four SIVagm viruses from wild-caught West African green monkeys were isolated and analyzed biologically and molecularly. Amplification, cloning, and sequencing of a 279-bp polymerase fragment directly from uncultured peripheral blood mononuclear cells was facilitated by the use of nested polymerase chain reaction. The results indicated that West African green monkeys are naturally infected with SIVs which are closely related to East African SIVagm isolates. However, structural, antigenic, and genetic differences were observed which strongly suggest that the West African green monkey viruses comprise a phylogenetically distinct subgroup of SIVagm. These findings support our previous hypothesis that SIVagm viruses may have evolved and diverged coincident with the evolution and divergence of their African green monkey host. In addition, this study describes a polymerase chain reaction-based approach that allows the identification and molecular analysis of divergent SIV strains directly from primary monkey tissue. This approach, which does not depend on virus isolation methods, should facilitate future studies aimed at elucidating the origins and natural history of SIVs in feral African green monkey populations.
Memrisor Based Computation-in-Memory Architecture for Data-Intensive Applications (2015)

One of the most critical challenges for today's and future data-intensive and big-data problems is data storage and analysis. This paper first highlights some challenges of the new born Big Data paradigm and shows that the increase of the data size has already surpassed the capabilities of today's computation architectures suffering from the limited bandwidth, programmability overhead, energy inefficiency, and limited scalability. Thereafter, the paper introduces a new memristor-based architecture for data-intensive applications. The potential of such an architecture in solving data-intensive problems is illustrated by showing its capability to increase the computation efficiency, solving the communication bottleneck, reducing the leakage currents, etc. Finally, the paper discusses why memristor technology is very suitable for the realization of such an architecture; using memristors to implement dual functions (storage and logic) is illustrated.
Acetabular imprinting device (AID) improves acetabular component positioning: a Sawbones® study. (2014)

The purpose of this study was to define the ability of a novel acetabular positioning device with 3D preoperative planning (AID) to improve acetabular component placement in total hip arthroplasty. Four surgeons placed the acetabular component in two Sawbones® models using three different methods: standard method, 3D planning method, and the AID method. The AID significantly decreased the mean deviation of actual acetabular component inclination from the preoperative plan when compared with standard and 3D planning methods (p = 0.003). Overall, AID reduced the number of malpositioned implants to 12.5%, compared with 87.5% in the standard method and 75% in the 3D planning method without use of the AID (p = 0.005). A clinical trial is needed to compare AID to standard surgical techniques.
Data from Genomic Evolutionary Patterns of Leiomyosarcoma and Liposarcoma (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Leiomyosarcoma and liposarcoma are common subtypes of soft tissue sarcoma (STS). Patients with metastatic leiomyosarcoma or dedifferentiated liposarcoma (DDLPS) typically have worse outcomes compared with localized leiomyosarcoma or well-differentiated liposarcoma (WDLPS). A better understanding of genetic changes between primary/metastatic leiomyosarcoma and between WDLPS/DDLPS may provide insight into their genetic evolution.&lt;/p&gt;Experimental Design:&lt;p&gt;We interrogated whole-exome sequencing (WES) from “trios” of normal tissue, primary tumor, and metastatic tumor from individual patients with leiomyosarcoma (&lt;i&gt;n&lt;/i&gt; = 9), and trios of normal tissue, well-differentiated tumor, and dedifferentiated tumor from individual patients with liposarcoma (&lt;i&gt;n&lt;/i&gt; = 19). Specifically, we performed mutational, copy number, and tumor evolution analyses on these cohorts and compared patterns among leiomyosarcoma and liposarcoma trios.&lt;/p&gt;Results:&lt;p&gt;Leiomyosarcoma cases harbored shared drivers through a typical parent/child relationship where the metastatic tumor was derived from the primary tumor. In contrast, while all liposarcoma cases shared the characteristic focal chromosome 12 amplicon, most paired liposarcoma cases did not share additional mutations, suggesting a divergent evolutionary pattern from a common precursor. No highly recurrent genomic alterations from WES were identified that could be implicated as driving the progression of disease in either sarcoma subtype.&lt;/p&gt;Conclusions:&lt;p&gt;From a genomic perspective, leiomyosarcoma metastases contain genetic alterations that are also found in primary tumors. WDLPS and DDLPS, however, appear to divergently evolve from a common precursor harboring 12q amplification, rather than as a transformation to a higher-grade tumor. Further efforts to identify specific drivers of these distinct evolutionary patterns may inform future translational and clinical research in STS.&lt;/p&gt;&lt;/div&gt;
MON-476 Growth Hormone and the Glomerular Podocyte: Studies of Podocyte-Specific Growth Hormone Receptor Gene Deletion in Mice (2019)

Previous research has suggested a role for growth hormone (GH) in the development of kidney disease. Evidence of increased glomerular size and sclerosis in bovine GH (bGH) overproducing animals suggests that excess GH action may cause or exacerbate glomerular damage. Within the glomerulus, the podocyte plays the role of forming a filtration barrier called the slit diaphragm. This cell is known to be dysfunctional in many models of nephropathy and is also a direct target of GH. To explore the mechanisms by which GH impacts the glomerulus, we have developed a transgenic mouse, the podocyte-specific GH receptor gene-disrupted mouse (podGHR-/-). These mice were generated on a C57BL/6J background using Cre-Lox transgenic methods. To examine the effects of high GH levels on the podocyte, these mice were crossed with bovine GH (bGH) overproducing mice and studied at several time points over the course of a year, alongside wild-type control mice and podGHR-/- mice lacking bGH overexpression. Various metabolic and physiologic assays were performed on these mice, including glomerular filtration rate (GFR) testing, glucose and insulin tolerance testing, body composition analysis, and urine & serum analysis. Histological analyses were also performed. Podocyte-specific GHR gene-deletion was associated with increased GFR in male podGHR-/- mice at 54 weeks of age, and with decreased GFR in male podGHR-/- mice with bGH overexpression at 54 weeks of age. PodGHR-/- male mice exhibited significantly decreased total kidney hydroxyproline content at 54 weeks of age as well as decreased glomerular trichrome stain deposition. Both male and female podGHR-/- mice showed decreased glomerular periodic acid Schiff stain deposition at 54 weeks of age. These results suggest a role for podocyte GH activity in the regulation of GFR in the aging and diseased kidney, as well as a role for GH in directing the deposition of collagen and glycosaminoglycans in glomerulus via the podocyte.
Vitamine D et santé osseuse (2014)

Le calcium est l’élément déterminant de la qualité du squelette parce qu’il lui confère ses propriétés de rigidité. Ainsi, en raison de l’enjeu majeur de santé publique représenté par les atteintes de l’appareil locomoteur chez les séniors, l’optimisation du statut calcique doit donc être assurée par la couverture des besoins définis par les apports nutritionnels conseillés, mais aussi par une potentialisation de sa biodisponibilité. Par conséquent, toute stratégie capable de favoriser l’absorption calcique doit être considérée. C’est pourquoi, la consommation alimentaire de calcium, ainsi que toute calcithérapie, doit être associée à la vitamine D qui, sous sa forme di-hydroxylée, intervient dans le mécanisme de transport actif du minéral à travers la paroi entérocytaire. Ce concept bénéficie d’un consensus et est solidement établi. D’autre part, des études récentes indiquent que la 25(OH)D pourrait directement moduler les cellules osseuses qui possèdent, non seulement des récepteurs spécifiques (VDR), mais aussi la 1α-hydroxylase nécessaire à la transformation de la molécule en son métabolite actif. En ce qui concerne la démonstration des effets osseux de la vitamine D, il est évident que l’hyperparathyroïdisme secondaire qui se développe lors d’une déficience du statut en vitaminique D est extrêmement délétère puisque qu’elle engendre une accélération de la résorption. C’est la raison pour laquelle, en situation de carence, une supplémentation peut améliorer le remodelage et la masse osseuse. Toutefois, l’effet reste faible. En revanche, les scientifiques s’accordent à considérer qu’une supplémentation associant calcium et vitamine D peut réduire le risque de fracture, l’intensité dépendant notamment du seuil initial de consommation, de la dose prescrite et bien sûr de l’observance du traitement. Plusieurs méta-analyses ont pu confirmer ces travaux initiaux. Cette apparente disparité entre la masse osseuse et le risque fracturaire pourrait s’expliquer par le cumul des effets de la vitamine sur le squelette avec l’impact exercé sur des cibles extra-osseuses comme, par exemple, le muscle, puisque le risque de chute diminue lors d’une prise en charge vitaminique. En outre, selon des données récentes, la vitamine D pourrait également réduire la masse adipeuse et l’insulino-résistance qui sont aussi des facteurs de risque pour la santé osseuse. En résumé, même si tous les mécanismes cellulaires et moléculaires ne sont pas totalement élucidés, le bénéfice d’une supplémentation en vitamine D est réel chez la personne carencée (en particulier le sujet âgé). Il est donc évident qu’il faut être vigilant au respect des recommandations. De plus, une correction des déficiences éventuelles devrait précéder ou accompagner toute thérapeutique en matière de pathologies osseuses.
Quinoline oxidoreductase from Pseudomonas putida 86: An improved purification procedure and electron paramagnetic resonance spectroscopy (1993)

Quinoline oxidoreductase, an iron-sulfur molybdenum flavoprotein containing flavin adenine dinucleotide and molybdopterin cytosine dinucleotide, was purified from Pseudomonas putida 86 to homogeneity. The various electron-transfer centers of the purified enzyme were examined by electron paramagnetic resonance spectroscopy. Quinoline deuterated at position 2 was prepared by deuterodecarboxylation of 2-quinolinecarboxylic acid. Quinoline added to the enzyme elicited the Mo(V) "rapid" type Q signal arising from the complex of enzyme and substrate, whereas in oxidized quinoline oxidoreductase a Mo(V) "resting" signal was observed. EPR spectroscopy at helium temperatures below 70 K revealed the existence of two types of iron-sulfur centers, Fe-S I and Fe-S II. An organic free radical appeared upon reduction with sodium dithionite. Inactivation of the enzyme by cyanide led to the inactive desulfo quinoline oxidoreductase, which yielded another Mo(V) signal designated "slow" type Q upon reduction with dithionite. Desulfo quinoline oxidoreductase was partially reactivated by incubation with sulfide.
Performance Assessment of Using Thermoelectric Generators for Waste Heat Recovery from Vapor Compression Refrigeration Systems (2021)

This article reports on an experimental analysis and performance assessment of using thermoelectric generators (TEGs) for waste heat recovery from residential vapor compression refrigeration systems. The analysis shows that there is a good opportunity for waste heat recovery using TEGs by de-superheating refrigerant after the compressor. Design and manufacturing of a de-superheater unit consisting of a tube and plate heat exchanger and thermoelectric generator modules (HE-TEGs) have been performed and integrated in an experimental test rig of R134a refrigeration cycle. Experimental assessment of the performance parameters, as compared to the basic refrigeration system, reveals that the overall coefficient of performance (COP) using HE-TEGs desuperheater unit increases by values ranging from 17% to 32% depending on the condenser and evaporator loads. Exergy analysis shows that the enhancement is attributed to reduction in the exergy destruction in the condenser and compressor due to lower values of condenser pressure and pressure ratio of the compressor. The output power of the HE-TEGs unit is found to be sufficient for driving the TEGs heat sinks air cooling fan, thus providing a passive de-superheating system without an additional external source of electricity. Further enhancement of the refrigeration cycle performance can be achieved by installation of additional HE-TEGs units.
Rekanalisation thrombosierter Hämodialyse-Shunts mit Oszillations-Aspiration und Maschenkorb (1993)

Three thrombosed hemodialysis shunts (two polytetrafluorethylene [Goretex] forearm shunts and one Brescia-Cimino shunt) were recanalized by an 8-F oscillational aspiration thrombectomy catheter. The total aspirated blood volume was less than 200 ml in each case. Subsequently, residual wall adherent thrombi were removed by means of a 6-F mesh basket catheter. The mesh basket showed optimal adaptation even to bent vessel or graft segments. The first experience with oscillational aspiration thrombectomy and mesh basket treatment in thrombosed hemodialysis shunts indicate that this technique may serve as a promising alternative to fibrinolysis or surgical shunt declotting.
Augmented Twin-Nonlinear Two-Box Behavioral Models for Multicarrier LTE Power Amplifiers (2014)

A novel class of behavioral models is proposed for LTE-driven Doherty power amplifiers with strong memory effects. The proposed models, labeled augmented twin-nonlinear two-box models, are built by cascading a highly nonlinear memoryless function with a mildly nonlinear memory polynomial with cross terms. Experimental validation on gallium nitride based Doherty power amplifiers illustrates the accuracy enhancement and complexity reduction achieved by the proposed models. When strong memory effects are observed, the augmented twin-nonlinear two-box models can improve the normalized mean square error by up to 3 dB for the same number of coefficients when compared to state-of-the-art twin-nonlinear two-box models. Furthermore, the augmented twin-nonlinear two-box models lead to the same performance as previously reported twin-nonlinear two-box models while requiring up to 80% less coefficients.
Biofiltration of volatile pollutants: Engineering mechanisms for improved design, long-term operation, prediction, and implementation. 1997 annual progress report (1997)

'Biofiltration systems can be used to treat volatile organic compounds (VOCs); however, the systems are poorly understood and are currently operated as black boxes. Common operational problems associated with biofilters include fouling, deactivation, and overgrowth, all of which make biofilters ineffective for continuous, long-term use. The objective of this investigation is to develop generic methods for long-term stable operation, in particular by using selective limitation of supplemental nutrients while maintaining high activity and the ability to regenerate biofilter activity. As part of this effort, the authors will provide a deeper fundamental understanding of the important biological and transport mechanisms in biodestruction of sparingly soluble VOCs and will extend this engineering approach and developed mathematical models to two additional systems of high-priority environmental management (EM) relevance-direct degradation and cometabolic degradation of priority pollutants such as BTEX (benzene, toluene, ethylbenzene, and xylene) and TCE (trichioroethylene), respectively. Preliminary results indicate that the author can control overgrowth of the biofilm while sustaining high degradation rates and develop basic predictive models that elucidate mass transfer and kinetic limitations in this system for alkanes. The alkanes are degraded into CO, and waterwith minimal biomass (due to the methodology proposed). This system will be used to test and model additional supplemental nutrient feeding strategies as well as methods to increase the fundamental driving forces by modification of the system. Models will be extended to non-steady-state, long-term operation. The author will examine the nature of the mixed microbial community in the VOC-degrading biofilm and test for new degradative activities. He will use cosolvents with surfactant properties to enhance hydrocarbon solubility in the biofilm and evaluate their impact on mass transfer and reaction rate in an operating biofilter. These results will point to further potential improvements in systems of EM priority. Constructed and acclimated three trickling-bed biofilters. Measured kinetic activity and mass transfer in biofilters under study. Demonstrated extended activity of biofilters in absence of supplemental nutrient. Quantified filter regeneration after prolonged starvation. Demonstrated competence of microbial consortium for degrading a variety of C, to C, alkanes as sole carbon and energy sources. Demonstrated competence of microbial consortium for degrading chlorinated alkane as sole carbon and energy sources. Examined solubility enhancement agents. Completed mathematical modeling of biofilm diffusion, reaction, and mass transfer effects for simple cases.'
Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor (2001)

Heterologous expression of the human neurotensin receptor type I (hNT1-R) has been achieved in the yeast Saccharomyces cerevisiae. Immunoanalysis of membranes prepared from cells expressing a c-myc-tagged version of hNT1-R revealed multiple c-myc cross-reacting polypeptides of high molecular mass, suggesting that hNT1-R was glycosylated in yeast. High-affinity binding sites for 125I-labeled-[monoiodo-Tyr3]neurotensin ([125I-Tyr3]NT) were detected on hNT1-R-expressing cells with Kd and Bmax values of 3.2 nM and of 500 receptors per cell, respectively. Competition binding studies of neurotensin with SR142948 and SR48692, two nonpeptidic antagonists of hNT1-R, indicated that the yeast-produced recombinant receptor displayed the same pharmacological properties as hNT1-R expressed in mammalian cells. Interestingly, neurotensin activated the pheromone pathway in hNT1-R-expressing cells in a dose-dependent fashion, as revealed by a beta-galactosidase activity assay with a pheromone-responsive Fus1:lacZ construct. Mutational inactivation of the SST2 and STE2 genes increased the level of beta-galactosidase activity in response to neurotensin by twofold. Recombinant hNT1-R-producing cells, which lacked the endogenous G-protein-coupled receptor for the alpha pheromone, mated with wild-type MATalpha haploid cells in response to neurotensin, leading to bona fide diploid zygote formation. This is the first report of a mammalian receptor that can replace the endogenous pheromone receptor when produced in yeast, by signaling a fully effective, agonist-induced, mating process.
Tunable Radiation Response in Hybrid Organic–Inorganic Gate Dielectrics for Low-Voltage Graphene Electronics (2016)

Solution-processed semiconductor and dielectric materials are attractive for future lightweight, low-voltage, flexible electronics, but their response to ionizing radiation environments is not well understood. Here, we investigate the radiation response of graphene field-effect transistors employing multilayer, solution-processed zirconia self-assembled nanodielectrics (Zr-SANDs) with ZrOx as a control. Total ionizing dose (TID) testing is carried out in situ using a vacuum ultraviolet source to a total radiant exposure (RE) of 23.1 μJ/cm(2). The data reveal competing charge density accumulation within and between the individual dielectric layers. Additional measurements of a modified Zr-SAND show that varying individual layer thicknesses within the gate dielectric tuned the TID response. This study thus establishes that the radiation response of graphene electronics can be tailored to achieve a desired radiation sensitivity by incorporating hybrid organic-inorganic gate dielectrics.