gebhart/patrepeval huggingface dataset:
6. Targeted Genome Editing of Cell Lines for Improved and Scalable Production of Lentiviral Vectors for Human Gene Therapy (2015)

Lentiviral vectors (LVs) represent efficient and versatile vehicles for gene therapy. The manufacturing of clinical-grade LVs relies on transient transfection of vector components. This method is labor and cost intensive and becomes challenging when facing the need of scale-up and standardization. The development of stable LV producer cell lines will greatly facilitate overcoming these hurdles. We have generated an inducible LV packaging cell line, carrying the genes encoding for third-generation vector components stably integrated in the genome under the control of tetracycline-regulated promoters. In order to minimize the immunogenicity of LVs for in vivo administration, we set out to remove the highly polymorphic and antigenic class-I major histocompatibility complex (MHC-I) expressed on LV packaging cells and subsequently incorporated on the LV envelope. We performed genetic disruption of the β-2 microglobulin (B2M) gene, a required component for the assembly and trafficking of the MHC-I to the plasma membrane in LV producer cells, exploiting the RNA-guided Cas9 nuclease. We generated B2M-negative cells devoid of surface-exposed MHC-I, which retain the ability to produce LVs. In order to insert the LV genome of interest in the packaging cell line, we performed site-specific integration in predetermined loci of the genome of these cells, chosen for robust expression, exploiting artificial nucleases and homology-directed repair. In several independent iterations of this process, we generated producer cell lines both for LV expressing marker genes and a therapeutic gene, i.e. coagulation factor IX (FIX), the gene mutated in hemophilia B. We show that these LV producer cells are stable in culture and can produce several liters of LV-containing conditioned medium. These LVs have comparable or only slightly lower infectious titer and specific infectivity than LVs produced by state-of-the-art transient transfection process and can transduce therapeutically relevant target cells, such as hematopoietic stem/progenitor cells and T lymphocytes to high efficiency. Moreover, we intravenously administered FIX-expressing LVs produced by the cell line to hemophilia B mice and established therapeutic levels of circulating FIX. These data indicate that site-specific integration is an efficient, rapid and reproducible method to generate LV producer cells, starting from a universal stable inducible LV packaging cell line. Overall, we provide evidence that rationally designed targeted genome engineering can be used to improve the quality, safety and sustainability of LV production for clinical use.
Multi-dimensional locks with on-line allocation schemes (2002)

Synchronization is inherent to parallel computing and comprises many aspects. One aspect is the access control to shared data, especially important in MIMD shared-memory architectures. Several locking mechanisms have been proposed to perform this task. Most of these schemes rely on very little hardware support, such as atomic read-modify-write operations. Today, the amount of hardware required to implement a locking mechanism is not a major constraint and will be even less important in the future. This makes it interesting to investigate schemes with more flexibility, better performance, and improved ease of use, that rely more on hardware assisted circuits than previous suggestions. In this paper multi-dimensional locking schemes that allocate locks on-line are presented. A lock is assigned to the access control of a data structure only during the time this structure needs to be locked. Three specific schemes are proposed. Two offer the possibility of locking sub-structures within multi-dimensional arrays. All three schemes protect locked structures against accesses of misbehaving threads.
Sub-Diffraction Limited Pattering via Optical Saturable Transformations (2011)

Here, we report on a method that resolves nanoscale patterns by exploiting the transitions of organic photochromic derivatives induced by their photoisomerization at low light intensities. Optically saturating such transitions enable patterning of features below the Abbé diffraction limit. We call this novel method Patterning via Optical Saturable Transformations (POST). In addition to its high resolution, POST has the potential for high throughput and low overall cost.
Identification and characterization of a new multigene family in the human MHC: A candidate autoimmune disease susceptibility element (3.8-1) (1994)

An association between idiopathic hemochromatosis (HFE) and the HLA-A3 locus has been previously well-established. In an attempt to identify potential HFE candidate genes, a genomic DNA fragment distal to the HLA-A9 breakpoint was used to screen a B cell cDNA library; a member (3.8-1) of a new multigene family, composed of five distinct genomic cross-reactive fragments, was identified. Clone 3.8-1 represents the 3{prime} end of 9.6 kb transcript which is expressed in multiple tissues including the spleen, thymus, lung and kidney. Sequencing and genome database analysis indicate that 3.8-1 is unique, with no homology to any known entries. The genomic residence of 3-8.1, defined by polymorphism analysis and physical mapping using YAC clones, appears to be absent from the genomes of higher primates, although four other cross-reactivities are maintained. The absence of this gene as well as other probes which map in the TNF to HLA-B interval, suggest that this portion of the human HMC, located between the Class I and Class III regions, arose in humans as the result of a post-speciation insertional event. The large size of the 3.8-1 gene and the possible categorization of 3.8-1 as a human-specific gene are significant given the genetic data that placemore » an autoimmune susceptibility element for IDDM and myasthenia gravis in the precise region where this gene resides. In an attempt to isolate the 5{prime} end of this large transcript, we have constructed a cosmid contig which encompasses the genomic locus of this gene and are progressively isolating coding sequences by exon trapping.« less
Effect of cation on the quantum efficiency and the photoreaction pathways of [W(CO)5X]? anions (1978)

The quantum efficiencies and product distrbutions for ligand photosubstitution and co-ordinated ligand photosubstitution reactions of anionic [W(CO)5X]–(X = Br, NCO, or N3) in CHCl3 vary by >300% when the cation is changed in the series Li+, AsPh4+, PPN+, and NEt4+[PPN =µ-nitrido-bis(triphenylphosphorus)].
Responses of LNCaP prostatic adenocarcinoma cell cultures to LY300502, a benzoquinolinone human type I 5α-reductase inhibitor (1996)

We evaluate the metabolic inhibitory, antiproliferative, and antisecretory effects of LY300502, a benzoquinolinone human-specific type I-selective steroid 5alpha-reductase inhibitor in LNCaP human prostatic adenocarcinoma cell cultures. Reductive metabolism of [3H-T] in the LNCaP cells was inhibited in a concentration-dependent manner by LY300502 (IC50 approximately 5.77 nM). The proliferative responses of LNCaP cells to LY300502 were examined in the presence of 0.1 NM testosterone (T), a concentration that stimulates maximal LNCaP cell numbers 40% above control levels. LY300502 significantly anatagonized T-induced stimulation of LNCaP cellular proliferation at concentrations greater that 10 nM (P<0.05), and at 1,000 nMcompletely blocked the mitogenic effects of T on LNCaP cells. In the absence of androgen, LY300502 had no effect on LNCaP cellular proliferation. In the presence of 100 nM T, an androgen concentration that maximally stimulates in vitro PSA production, LY300502 significantly antagonized T-induced PSA secretion at a concentration equal to or greater than 30 nM (P<0.05). These studies provide the basis for additional investigations into the pathophysiologic significance of type I 5alpha-reductase to prostatic cancer and the potential utility of selective inhibitors as therapeutic agents.
Import of rat ornithine transcarbamylase precursor into mitochondria: two-step processing of the leader peptide. (1987)

The mitochondrial matrix enzyme ornithine transcarbamylase (OTC) is synthesized on cytoplasmic polyribosomes as a precursor (pOTC) with an NH2-terminal extension of 32 amino acids. We report here that rat pOTC synthesized in vitro is internalized and cleaved by isolated rat liver mitochondria in two, temporally separate steps. In the first step, which is dependent upon an intact mitochondrial membrane potential, pOTC is translocated into mitochondria and cleaved by a matrix protease to a product designated iOTC, intermediate in size between pOTC and mature OTC. This product is in a trypsin-protected mitochondrial location. The same intermediate-sized OTC is produced in vivo in frog oocytes injected with in vitro-synthesized pOTC. The proteolytic processing of pOTC to iOTC involves the removal of 24 amino acids from the NH2 terminus of the precursor and utilizes a cleavage site two residues away from a critical arginine residue at position 23. In a second cleavage step, also catalyzed by a matrix protease, iOTC is converted to mature OTC by removal of the remaining eight residues of leader sequence. To define the critical regions in the OTC leader peptide required for these events, we have synthesized OTC precursors with alterations in the leader. Substitution of either an acidic (aspartate) or a "helix-breaking" (glycine) amino acid residue for arginine 23 of the leader inhibits formation of both iOTC and OTC, without affecting translocation. These mutant precursors are cleaved at an otherwise cryptic cleavage site between residues 16 and 17 of the leader. Interestingly, this cleavage occurs at a site two residues away from an arginine at position 15. The data indicate that conversion of pOTC to mature OTC proceeds via the formation of a third discrete species: an intermediate-sized OTC. The data suggest further that, in the rat pOTC leader, the essential elements required for translocation differ from those necessary for correct cleavage to either iOTC or mature OTC.
Three-Dimensional Quantitative Structure−Activity Relationship Analysis of Ligand Binding to Human Sequence Antidigoxin Monoclonal Antibodies Using Comparative Molecular Field Analysis (2002)

The present study indicates that the newly generated human sequence antidigoxin monoclonal antibody (mAb), 1B3, binds digoxin with a different fine specificity binding than our previously obtained human sequence monoclonal antibodies (mAbs) (Ball, W. J.; et al. J. Immunol. 1999, 163, 2291−2298). Uniquely, 1B3 has a higher affinity for digitoxin than digoxin, the immunizing hapten, and a strong requirement for at least one sugar residue linked to the aglycone (-genin). By means of comparative molecular field analysis (CoMFA), the results of competition binding studies for 56 cardiotonic and hormonal steroids were employed to develop three-dimensional quantitative structure−activity relationship (3D-QSAR) models for ligand binding to 1B3 and to three additional human sequence mAbs, as well as the murine antidigoxin mAb 40-50 (Mudgett-Hunter, M.; et al. Mol. Immunol. 1985, 22, 447−488). All five 3D-QSAR models yielded cross-validated q2 values greater than 0.5, which indicates that they have significant predictive ability. The CoMFA StDev*Coeff contour plots, as well as the competition results, indicate that 1B3 binds ligands in a manner distinct from the other four mAbs. The CoMFA contour plots for 40-50 were also compared with the known X-ray crystallographic structure of the 40-50−ouabain complex (Jeffrey, P. D.; et al. J. Mol. Biol. 1995, 248, 344−360) in order to identify correlations between residues in the mAb binding site and specific contour plot regions. These 3D-QSAR models and their respective contour plots should be useful tools to further understand the molecular nature of antibody−antigen interactions and to aid in the redesign or enhancement of therapeutic antibodies.
Superplasticity in Mg–Li–Zn Alloys Processed by High Ratio Extrusion (2008)

Abstract Superplastic behavior of Mg-8.5Li-1Zn and Mg-8.5Li-3Zn alloys has been investigated. Dynamic recrystallization occurs in the Mg–Li–Zn alloys during extruding with high ratio after stir casting. Mg-8.5Li-1Zn alloy exhibits an elongation of about 400% at the high strain rate of 1.1 × 10−2 S−1 at 623 K, while the Mg-8.5Li-3Zn alloy shows maximum elongation of more than 540%. The apparent activation energy for superplastic flow of both Mg-8.5Li-1Zn and Mg-8.5Li-3Zn alloys at 573–673 K is about 86 kJ/mol and 79 kJ/mol, respectively, so that the dominant deformation mechanism in Mg–Li–Zn alloys is grain boundary sliding (GBS) controlled by grain boundary diffusion. Keywords: Activation energyElongationExtrusionFractureGrain boundaryMagnesium alloysMagnesium–lithium alloyMetallographic phasesPlastic flowRecrystallizationSlidingStirring castingStrain rateSuperplasticityTensile testing ACKNOWLEDGMENT One of the authors (Shangli Dong) gratefully appreciates the financial support from Japan Society for the Promotion of Science (JSPS).
Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data (2014)

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.
Effect of a Variable Prosthetic Neck-Shaft Angle and the Surgical Technique on Replication of Normal Humeral Anatomy (2009)

This study demonstrates the ability of both an adjustable and a fixed neck-shaft angle prosthesis to replicate humeral anatomy. However, the fixed-angle device requires specific modifications of the surgical technique to accommodate the specific prosthetic design and optimize the surgeon's ability to replicate normal anatomic parameters in humeri with an extreme neck-shaft angle.
Anisotropic electron mobility studies on Cl2-NDI single crystals and the\n role of static and dynamic lattice deformations upon temperature variation (2015)

The anisotropic electron transport in the (001) plane of sublimation-grown\nCl$_{2}$-NDI (naphthalene diimide) single crystals is analysed over a\ntemperature range between 175 K and 300 K. Upon cooling from room temperature\nto 175 K the electron mobility along the direction of preferred transport\nmonotonously increases from 1.5 cm$^{2}$/Vs to 2.8 cm$^{2}$/Vs according to a\ndistinct temperature relation of $~T^{-1.3}$. At first glance, these\ncharacteristics allude to a coherent, i.e. band-like charge carrier transport\npredominantly governed by inelastic scattering with accoustic phonons. However,\nas we will demonstrate, the experimental mobility data can be consistently\ndescribed within the framework of incoherent, hopping-type transport modeled by\nLevich-Jortner rates, explicitly accounting for the inner and outer relaxation\nenergies related to thermally induced lattice effects and enhanced\nelectron-phonon interaction at elevated temperatures. Complementary\nband-structure calculations yielding temperature dependent effective mass\ntensors deviate stronger from experimentally observed spatially anisotropic\ntransport behavior. Thus, these results hint at the fact that by the particular\ninterplay of the transport energies the mobility of a given organic\nsemiconducting material might appear to be band-like in a certain temperature\nregime even though the underlying charge carrier transport can be of\nincoherent, hopping-type nature. Building on this description, we further\nexplore the role of the intermolecular electronic coupling and develop a\nprocedure to distinguish between its dependence on static and dynamic lattice\ndeformation upon temperature variation.\n
Serum Albumin Level as a Predictor of Outcome in Traumatic Brain Injury: Potential for Treatment (2008)

Serum albumin level seems to be an independent predictor of poor outcome. The model also identified classic predictors of poor outcome that tends to strengthen its adequacy. Because albumin level is the only modifiable factor influencing outcome, it seems justified to carry out a randomized trial of the use of albumin in the treatment of brain injury.
CT and MR imaging evaluation of chest wall disorders. (1994)

Computed tomography (CT) and magnetic resonance (MR) imaging have complementary roles in the evaluation of chest wall disorders, which include mesenchymal tumors, primary and secondary malignancies, and inflammatory and infectious diseases. Important anatomic regions of the chest wall to evaluate on axial images include the supraclavicular fossa, axilla, and parasternal-internal mammary zone. For diagnosis of a suspected lipoma, CT is faster and less expensive; however, MR imaging may better delineate the extent of more invasive tumors if surgery is planned. MR imaging best depicts intramuscular neurofibromas and soft-tissue, intraspinal, and marrow involvement of neurogenic tumors, although CT more readily shows small calcifications and bone destruction. For diagnosis of lymphangioma, particularly when intravenous contrast material cannot be given for CT, MR imaging is preferred. CT more accurately demonstrates cortical bone destruction from masses arising in the ribs, but MR imaging is better for depicting infiltration of bone marrow and the extent of soft-tissue involvement. MR imaging displays Pancoast tumors and chest wall invasion from lung cancer better than CT because of its multiplanar capability and depiction of subtle differences in soft-tissue contrast. Both CT and MR imaging are helpful in evaluating infections, with CT being used to reveal bone destruction and to guide aspiration and drainage and MR imaging demonstrating soft-tissue involvement. The choice of technique, CT versus MR imaging, often depends on the specific clinical question to be addressed.
Elbow arthroscopy: indications, techniques, outcomes, and complications. (2015)

Elbow arthroscopy is a tool useful for the treatment of a variety of pathologies about the elbow. The major indications for elbow arthroscopy include débridement for septic elbow arthritis, synovectomy for inflammatory arthritis, débridement for osteoarthritis, loose body extraction, contracture release, treatment of osteochondral defects and selected fractures or instability, and tennis elbow release. To achieve favorable outcomes after elbow arthroscopy, the surgeon should be aware of contraindications, technical considerations, anatomic principles, and the need for proper patient positioning and portal selection. Elbow arthroscopy is an effective procedure for the treatment of inflammatory arthritis, osteoarthritis, and lateral epicondylitis.
<title>WEST (WDM and electronic switching technology) project: 40 Gb/s WDM system review</title> (1997)

Formed in January 1995, WEST is a DARPA-supported consortium investigating technologies for implementing add-drop and cross-connect switches operating at 10 Gbit/s. Using wavelength division multiplexing (WDM), each fiber supports 40 Gbit/s (4 by 10 Gbit/s) aggregate bandwidth for SONET/SDH operation. Consortium members include Rockwell Corporation, Ortel Corporation, UCSB, UCSD, UCLA, and Caltech/JPL.
Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect (2019)

Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (<b>1</b>) and polycerasoidin (<b>2</b>) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (<b>1</b>) and polycerasoidin (<b>2</b>), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (<b>1</b>) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure-activity relationship studies revealed that a free phenol group at C-6 and a carboxylic acid at C-9' were key features for dual PPARα/γ agonism activity. Molecular modeling indicated the relevance of these groups for optimal ligand binding to the PPARα and PPARγ domains. In addition, polycerasoidol (<b>1</b>) exhibited a potent anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium in a concentration-dependent manner via RXRα/PPARγ interactions. Therefore, polycerasoidol (<b>1</b>) can be considered a hit-to-lead molecule for the further development of novel dual PPARα/γ agonists capable of preventing cardiovascular events associated with metabolic disorders.
Abstract 15091: Clonogenic Human Cardiac Stem Cells With Long Telomeres Can Be Isolated From Minute Endomyocardial Biopsies (2013)

Autologous cardiac stem cell (CSC) therapy has been implemented in patients with chronic heart failure of ischemic origin. The right atrial appendage, weighing ~1 g, was used for the isolation and ...
Fullerene‐Based Acceptor Materials (2014)

This chapter contains sections titled: Introduction and Overview Fullerenes as n-Type Semiconductors Fullerene Derivatives Derivatives of C70 and C84 Fullerene Bisadducts Endohedral Compounds Commercialization of Fullerene Derivatives