gebhart/patrepeval huggingface dataset:
Retrovirus-Mediated Gene Transfer of NPM-ALK Causes Lymphoid Malignancy in Mice (1997)

Approximately 5% to 10% of all non-Hodgkin's lymphomas contain a t(2;5)(p23;q35) chromosomal rearrangement, which we have previously shown results in the generation of the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). To assess the transforming potential of NPM-ALK in an animal model, we infected 5-fluorouracil-treated murine bone marrow using retroviral stocks and transplanted this infected marrow into lethally irradiated BALB/cByJ mice. Male mice were transplanted with bone marrow from female donors at 10 weeks of age, with 7 of the animals receiving marrow infected with a retroviral construct, pSR alphaMSVtkneo-NPM-ALK, that contains the human NPM-ALK cDNA, and 4 serving as a control group, receiving "empty" pSR alphaMSVtkneo-infected marrow. Whereas all mice in the control group were alive and well up to 11 months after transplantation, 4 of the 7 mice transplanted with marrow containing the NPM-ALK construct developed lymphoma within 4 to 6 months. Tumors arose in the mesenteric lymph nodes, with metastases to the lungs, kidneys, liver, spleen, and the paraspinal area. When cells from the tumors and bone marrow were transplanted into sublethally irradiated secondary recipients, 10 of these 13 mice developed tumors within 9 months. Immunoblot analysis of cell lysates using an ALK polyclonal antibody showed NPM-ALK expression in all tumors examined. Histologically, the tumors were composed of a uniform population of large immunoblastic cells with basophilic cytoplasm, centrally placed nuclei, and distinct nucleoli. Genotypic analysis showed that the tumors were B-lineage and clonal, with rearrangements of the Ig heavy- and kappa light-chain loci and no rearrangements of the T-cell receptor beta locus. Immunocytochemical studies confirmed the presence of IgM heavy chains and kappa light chains within the tumor cells. Thus, in this retroviral gene transfer model, NPM-ALK expression in mice causes B-lineage large-cell lymphoma, suggesting a direct causative role for this activated fusion tyrosine kinase in human lymphoma.
Engineered Luciferase Reporter from a Deep Sea Shrimp Utilizing a Novel Imidazopyrazinone Substrate (2012)

Bioluminescence methodologies have been extraordinarily useful due to their high sensitivity, broad dynamic range, and operational simplicity. These capabilities have been realized largely through incremental adaptations of native enzymes and substrates, originating from luminous organisms of diverse evolutionary lineages. We engineered both an enzyme and substrate in combination to create a novel bioluminescence system capable of more efficient light emission with superior biochemical and physical characteristics. Using a small luciferase subunit (19 kDa) from the deep sea shrimp Oplophorus gracilirostris, we have improved luminescence expression in mammalian cells ~2.5 million-fold by merging optimization of protein structure with development of a novel imidazopyrazinone substrate (furimazine). The new luciferase, NanoLuc, produces glow-type luminescence (signal half-life >2 h) with a specific activity ~150-fold greater than that of either firefly (Photinus pyralis) or Renilla luciferases similarly configured for glow-type assays. In mammalian cells, NanoLuc shows no evidence of post-translational modifications or subcellular partitioning. The enzyme exhibits high physical stability, retaining activity with incubation up to 55 °C or in culture medium for >15 h at 37 °C. As a genetic reporter, NanoLuc may be configured for high sensitivity or for response dynamics by appending a degradation sequence to reduce intracellular accumulation. Appending a signal sequence allows NanoLuc to be exported to the culture medium, where reporter expression can be measured without cell lysis. Fusion onto other proteins allows luminescent assays of their metabolism or localization within cells. Reporter quantitation is achievable even at very low expression levels to facilitate more reliable coupling with endogenous cellular processes.
Dielectric Relaxation Spectroscopy of Lysozyme Aqueous Solutions: Analysis of the δ-Dispersion and the Contribution of the Hydration Water (2011)

The dielectric properties of lysozyme aqueous solutions have been investigated over a wide frequency range, from 1 MHz to 50 GHz, where different polarization mechanisms, at a molecular level, manifest. The dielectric relaxation spectra show a multimodal structure, reflecting the complexity of the protein-water interactions, made even more intricate with the increase of the protein concentration. The deconvolution of the spectra into their different components is not unambiguous and is generally a delicate process which requires caution. We have analyzed the whole relaxation region, on the basis of the sum of simple Debye-type relaxation functions, considering three main contributions. Particular attention has been payed to the δ-dispersion, intermediate between the β-dispersion (rotational dynamics of the protein) and the γ-dispersion (orientational polarization of the water molecules). This intermediate contribution to the dielectric spectrum is attributed to the orientational polarization of water molecules in the immediate vicinity of the protein surface (hydration water). Our measurements clearly demonstrate that, at least at high protein concentrations, the δ-dispersion has a bimodal structure associated with two kinds of hydration water, i.e., tightly bound and loosely bound hydration water. In the concentration range investigated, the existence of a three-modal δ-dispersion, as recently suggested, is not supported, on the basis of statistical tests, by the analysis of the dielectric relaxations we have performed and a bimodal dispersion is accurate enough to describe the experimental data. The amount of the hydration water has been evaluated both from the dielectric parameters associated with the δ-dispersion and from the decrement of the loss peak of the γ-dispersion. The relative weight of tightly bound and loosely bound hydration water is briefly discussed.
Comparison of TCA and ICA techniques in fMRI data processing (2004)

TCA and ICA techniques are comparable in generating functional brain maps in event-related fMRI experiments. Although ICA has richer features in exploring the spatial and temporal information of the functional images, the TCA method has advantages in its computational efficiency, repeatability, and readiness to average data from group subjects
Input Devices and Interaction Techniques for Advanced Computing (1995)

One enduring trait of computing systems is the presence of the human operator. At the human-computer interface, the nature of computing has witnessed dramatic transformations—from feeding punched cards into a reader to manipulating 3D virtual objects with an input glove. The technology at our fingertips today transcends by orders of magnitude that in the behemoth calculators of the 1940s. Yet technology must co-exist with the human interface of the day. Not surprisingly, themes on keeping pace with advances in technology in the human-computer interface and, hopefully, getting ahead, underlie many chapters in this book. The present chapter is no exception. Input devices and interaction techniques are the human operator’s baton. They set, constrain, and elicit a spectrum of actions and responses, and in a large way inject a personality on the entire human-machine system. In this chapter, we will present and explore the major issues in “input,” focusing on devices, their properties and parameters, and the possibilities for exploiting devices in advanced human-computer interfaces. To place input devices in perspective, we illustrate a classical human-factors interpretation of the human-machine interface (e.g., Chapanis, 1965, p. 20). Figure 11-1 simplifies the human and machine to three components each. The internal states of each interact in a closed-loop system through controls and displays (the machine interface) and motor-sensory behaviour (the human interface). The terms “input” and “output” are, by convention, with respect to the machine; so input devices are inputs to the machine controlled or manipulated by human “outputs.” Traditionally human outputs are our limbs—the hands, arms, legs, feet, or head—but speech and eye motions can also act as human output. Some other human output channels are breath and electrical body signals (important for disabled users). Interaction takes place at the interface (dashed line in Figure 11-1) through an output channel—displays stimulating human senses—and the input channel. In the present chapter, we are primarily interested in controls, or input devices; but, by necessity, the other components in Figure 11-1 will to some extent participate in our discussion.
An arbitrary waveform stimulus circuit for visual prostheses using a low-area multibias dac (2003)

Attempts are underway to construct a retinal prosthesis to recover limited vision for blind patients with retinitis pigmentosa using implantable electronic devices. These microchips provide electrical stimulation to damaged retinal tissues using an array of stimulus circuits. This paper describes improvements to conventional circuit designs with significantly decreased implementation area and the ability to support arbitrary stimulus waveforms where an array of such stimulus circuits is required. This yields greater spatial resolution in stimulation owing to more stimulus circuits per chip area. Also introduced are digital-to-analog converter gain prescalar and dc-offset circuits which tune the stimulus circuits to an optimally effective range due to variation in retinal degradation. The prototype chip was fabricated by MOSIS in 1.2-μm CMOS technology.
Analysis of Backward Congestion Notification (BCN) for Ethernet In Datacenter Applications (2007)

IEEE 802.1 standards committee is working on a new specification for congestion notification in Ethernet networks. The goal of this work is to enable application of Ethernet in backend datacenter applications. Such applications typically use fiber channel and infiniband due to their loss-free characteristics. A backward congestion notification (BCN) scheme is one of the candidate schemes proposed to avoid long delays and minimize loss in Ethernet networks. This paper presents an analysis of this scheme. We develop an analytical model to analyze the stability and the rate of convergence of the scheme. It is shown that BCN achieves proportional fairness and not max-min fairness under certain circumstances. Simulation results are presented that validate the analytical results.
In vivo measurement of the photostability of sunscreen products using diffuse reflectance spectroscopy (2002)

Our study confirms the prediction of the in vitro methods previously used to assess the photostability of sunscreen products. In addition, DRS provides a powerful new tool for the in vivo simultaneous evaluation of photostability and estimation of the UVA protection factor of sunscreen products performed during the test for SPF determination.
In Vivo Correction of Complement Regulatory Protein Deficiency with an Inhibitor Targeting the Red Blood Cell Membrane (2005)

Because of the complement system's involvement in many human diseases and potential complications associated with its systemic blockade, site-specific regulation of this effector system is an attractive concept. We report on further developments of such an approach using a single-chain Ab fragment as a vehicle to deliver complement regulatory proteins to a defined cell type. In a model system in which RBCs deficient in complement receptor 1-related gene/protein y (Crry) are rapidly cleared after injection into wild-type animals by a complement-dependent mechanism, we selectively reconstituted these cells with N- and C-terminally targeted recombinant forms of Crry. Transfusion of Crry-coated knockout RBCs into C57BL/6 mice extended their in vivo half-life from <5 min to approximately 2 days. Maintenance of protective levels of Crry (by a combined treatment of donor and recipient RBCs) led to nearly normal RBC survival. Uniform in vitro and in vivo coating of the RBCs and the more efficient complement inhibitory capacity of C-terminally tagged Crry were other interesting features of this experimental system. These results suggest the possibility of using the single-chain Ab fragment-mediated targeting concept of complement regulatory proteins to restrict complement inhibition to the site of its excessive activation.
Large Area, 38 nm Half-Pitch Grating Fabrication by Using Atomic Spacer Lithography from Aluminum Wire Grids (2006)

We wrapped 150 nm period aluminum wire grid polarizer (WGP) with AlSiOx by using atomic layer deposition at 250 degrees C. The nanometer precision coating defined the spacer to double the spatial frequency of the 100 mm diameter grating fabricated by using a legacy immersion holography setup at 351 nm wavelength. Half-pitch grating of approximately 38 nm was demonstrated with good pattern uniformity, excellent repeatability, and a wide processing window. We believe 10 nm half-pitch grating over even larger areas are viable, overcoming one major hurdle to commercialize nanoimprint.
Bovine Surfactant Therapy for Patients With Acute Respiratory Distress Syndrome (1997)

Lung surfactant is deficient in patients with acute respiratory distress syndrome (ARDS). We performed a randomized, prospective, controlled, open-label clinical study of administration of a bovine surfactant to patients with ARDS to obtain preliminary information about its safety and efficacy. Patients received either surfactant by endotracheal instillation in addition to standard therapy or standard therapy only. Three different groups of patients receiving surfactant were studied: patients receiving up to eight doses of 50 mg phospholipids/kg, those receiving up to eight doses of 100 mg phospholipids/kg, and those receiving up to four doses of 100 mg phospholipids/kg. Outcome measures included ventilatory support parameters, arterial blood gases, organ system failures, bronchoalveolar lavage (BAL) analyses, immunologic analyses, survival, and adverse events during the 28-d study period. Fifty-nine study patients were evaluable; 43 in the surfactant group and 16 in the control group. The FI(O2) at 120 h after treatment began was significantly decreased only for patients who received up to four doses of 100 mg phospholipids/kg surfactant as compared with control patients (p = 0.011). Mortality in the same group of patients was 18.8%, as compared with 43.8% in the control group (p = 0.075). The surfactant instillation was generally well tolerated, and no safety concerns were identified. This pilot study presents preliminary evidence that surfactant might have therapeutic benefit for patients with ARDS, and provides rationale for further clinical study of this agent.
A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array (2004)

We present a high aspect ratio microfluidic device for culturing cells inside an array of microchambers with continuous perfusion of medium. The device was designed to provide a potential tool for cost-effective and automated cell culture. The single unit of the array consists of a circular microfluidic chamber 40 microm in height surrounded by multiple narrow perfusion channels 2 microm in height. The high aspect ratio (approximately 20) between the microchamber and the perfusion channels offers advantages such as localization of the cells inside the microchamber as well as creating a uniform microenvironment for cell growth. Finite element methods were used to simulate flow profile and mass transfer of the device. Human carcinoma (HeLa) cells were cultured inside the device with continuous perfusion of medium at 37 degrees C and was grown to confluency. The microfluidic cell culture array could potentially offer an affordable platform for a wide range of applications in high throughput cell-based screening, bioinformatics, synthetic biology, quantitative cell biology, and systems biology.
Construction of a retrovirus capable of transducing and expressing genes in multipotential embryonic cells. (1984)

Retroviral gene expression is inhibited in embryonal carcinoma (EC) cells. We have constructed a recombinant retroviral vector that is capable of expressing the neomycin-resistance (neo) gene in EC cells. The critical modification that permits expression of the neo gene is the insertion of a composite simian virus 40 early gene-herpes simplex virus type 1 thymidine kinase gene (SVtk) promoter 3' to the viral first intron and 5' to the neo gene. When the SVtk promoter is deleted, the recombinant retrovirus is either unable or extremely inefficient at expressing the neo gene in EC cells.
Free radical theory of autoimmunity (2006)

The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity.
Effect of N‐Acetyl‐cysteine, D‐Penicillamine and Buthionine Sulfoximine on Glutathione Levels and CNS Oxygen Toxicity in Rats (1990)

The effect of glutathione (GSH) synthesis modulators - L-buthionine sulfoximine (BSO), N-acetyl cysteine (NAC) and D-penicillamine (DPA) - on the susceptibility of rat CNS to O2 toxicity was investigated. The animals were given 5% sucrose or 40 mM solutions of BSO, NAC or DPA in 5% sucrose as drinking water for one week and sacrificed prior to or after exposure to 4.5 ATA O2. The GSH content in brain, liver, lung and blood, and the activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PD) and superoxide dismutase (SOD) in brain and lungs were measured. The brain GSH content and the enzyme activities were not changed by any of the drugs. BSO decreased the GSH content in all the other tissues; NAC and DPA treatments increased the GSH content in lungs, blood and/or liver. The CNS toxicity threshold as measured by the time of appearance of first electrical discharge (FED) on ECoG recording was not changed by NAC or DPA, but BSO brought about a significant delay in FED time. It is suggested that increased extracerebral GSH levels do not protect against CNS oxygen toxicity, and that BSO provides some protection, probably via a glutathione-independent mechanism.
Cationic lipids for reporter gene and CFTR transfer to rat pulmonary epithelium. (1995)

Increasing evidence indicates that cationic liposomes are capable of safely transferring foreign genes to pulmonary epithelium in vitro and in vivo. To transfer reporter genes and the cystic fibrosis transmembrane conductance regulator (CFTR) to mammalian respiratory epithelium we used two cationic lipid formulations: N-[1-(2,3-dioleoyloxy)propyl] N,N,N-triethylammonium chloride (DOTMA), and 1,2-dimyristyloxy-propyl-3-dimethylhydroxyethylammonium bromide (DMRIE) at a 1:1 molar ratio with dioleoyl phosphatidylethanolamine (DOPE). Lipid-DNA conjugates containing either CFTR or LacZ were instilled directly into the airways of Sprague-Dawley rats. Rats treated with LacZ cDNA in vivo demonstrated expression in 30-50% of the large and medium-sized airways, with some airways showing high efficiency gene transfer and expression (in the most proximal airways, 70-80% of surface epithelial cells were positive for expression of a nuclear targeted LacZ). While control and LacZ treated tracheas mounted in Ussing chambers showed minimal stimulation of transepithelial chloride (Cl)-currents by cAMP (suggesting low levels of endogenous rat CFTR activity), tracheas taken from animals receiving CFTR exhibited significant forskolin-stimulated currents at 72 h after gene transfer. Human CFTR gene expression was also detected by polymerase chain reaction (PCR) analysis of reverse transcribed lung RNA. These results, together with previous studies using lipid-mediated gene transfer in mice, help confirm the potential for cationic lipid-mediated gene transfer in the gene therapy of cystic fibrosis in humans.
Influence of Oxidation and Multimerization on the Immunogenicity of a Thioredoxin-L2 Prophylactic Papillomavirus Vaccine (2013)

Current commercial prophylactic human papillomavirus (HPV) vaccines are based on virus-like particles assembled from the major capsid protein L1 and show excellent safety and efficacy profiles. Still, a major limitation is their rather narrow range of protection against different HPV types. In contrast, the minor capsid protein L2 contains a so-called major cross-neutralizing epitope that can induce broad-range protective responses against multiple HPV types. This epitope is conserved among different papillomaviruses (PV) and contains two cysteine residues that are present in the L2 proteins of all known PV types. The main challenge in developing L2-directed vaccines is to overcome the intrinsically low immunogenicity of the L2 protein. Previously, we developed a recombinant L2-based prototype vaccine by inserting peptide epitopes spanning the cross-neutralizing L2 sequence into a bacterial thioredoxin (Trx) scaffold. These antigens induced high-titer neutralizing antibodies in mice. Here, we address the question of whether Trx scaffold multimerization may further enhance the immunogenicity of the TrxL2 vaccine. We also demonstrate that the oxidation state of the conserved cysteine residues is not essential for vaccine functionality, but it contributes to immunogenicity.
PPM: one step to practicality (2003)

PPM is one of the most promising lossless data compression algorithms using Markov source model of order D. Its main essence is the coding of a new (in the given context) symbol in one of inner nodes of the context tree; a sequence of the special escape symbols is used to describe this node. In reality, the majority of symbols is encoded in inner nodes and the Markov model becomes rather conventional. In spite of the fact that the PPM algorithm achieves the best results in comparison with others, it is used rarely in practical applications due to its high computational complexity. This paper is devoted to the PPM algorithm implementation that has a complexity comparable with widespread practical compression schemes based on LZ77, LZ78 and BWT algorithms. This scheme has been proposed by Shkarin (see Problems of Information Transmission, vol.34, no.3, p.44-54, 2001) and named PPM with information inheritance (PPMII).