gebhart/patrepeval huggingface dataset:
Optimized Production of High-Titer Recombinant Adeno-Associated Virus in Roller Bottles (2003)

Adeno-associated viral (AAV) vectors are used for in vivo gene transfer in a number of preclinical models of genetic diseases (including large-animal models) and are currently being tested in clinical trials for treatment of hemophilia B and cystic fibrosis. Protocols for production of AAV vectors in a helper virus-free system are available and are based on transient transfection of HEK-293 cells with multiple plasmids. Scale-up of vector production has been labor intensive and inefficient because of a lack of larger culture vessels suitable for growth of adherent cells, large-scale transfection, and vector production. Here we report efficient production of AAV vector in roller bottles, which represents a 10-fold scale-up from the conventional flask or plate method. Optimized production yielded greater than 10(13) vector genomes per bottle and was as cost effective as published protocols using plates. Successful vector production by this method was dependent on optimization of transfection by calcium phosphate precipitation, of monitoring of cell growth (by measurement of glucose consumption), of cell culture conditions, and CO2/air exchange with the culture vessel.
Memory representations underlying motor commands used during manipulation of common and novel objects (1993)

1. While subjects lifted a variety of commonly handled objects of different shapes, weights, and densities, the isometric vertical lifting force opposing the object's weight was recorded from an analog weight scale, which was instrumented with high-stiffness strain gauge transducers. 2. The force output was scaled differently for the various objects from the first lift, before sensory information related to the object's weight was available. The force output was successfully specified from information in memory related to the weight of common objects, because only small changes in the force-rate profiles occurred across 10 consecutive lifts. This information was retrieved during a process related to visual identification of the target object. 3. The amount of practice necessary to appropriately scale the vertical lifting and grip (pinch) force was also studied when novel objects (equipped with force transducers at the grip surfaces) of different densities were encountered. The mass of a test object that subjects had not seen previously was adjusted to either 300 or 1,000 g by inserting an appropriate mass in the object's base without altering its appearance. This resulted in either a density that was in the range of most common objects (1.2 kg/l) or a density that was unusually high (4.0 kg/l). 4. Low vertical-lifting and grip-force rates were used initially with the high-density object, as if a lighter object had been expected. However, within the first few trials, the duration of the loading phase (period of isometric force increase before lift-off) was reduced by nearly 50% and the employed force-rate profiles were targeted for the weight of the object.(ABSTRACT TRUNCATED AT 250 WORDS)
Filamentous Bacteriophage Fd as an Antigen Delivery System in Vaccination (2012)

Peptides displayed on the surface of filamentous bacteriophage fd are able to induce humoral as well as cell-mediated immune responses, which makes phage particles an attractive antigen delivery system to design new vaccines. The immune response induced by phage-displayed peptides can be enhanced by targeting phage particles to the professional antigen presenting cells, utilizing a single-chain antibody fragment that binds dendritic cell receptor DEC-205. Here, we review recent advances in the use of filamentous phage fd as a platform for peptide vaccines, with a special focus on the use of phage fd as an antigen delivery platform for peptide vaccines in Alzheimer's Disease and cancer.
Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses (2015)

Direct delivery of aerosolized vaccines to the respiratory mucosa elicits both systemic and mucosal responses. This vaccine strategy has not been tested for Ebola virus (EBOV) or other hemorrhagic fever viruses. Here, we examined the immunogenicity and protective efficacy of an aerosolized human parainfluenza virus type 3-vectored vaccine that expresses the glycoprotein (GP) of EBOV (HPIV3/EboGP) delivered to the respiratory tract. Rhesus macaques were vaccinated with aerosolized HPIV3/EboGP, liquid HPIV3/EboGP, or an unrelated, intramuscular, Venezuelan equine encephalitis replicon vaccine expressing EBOV GP. Serum and mucosal samples from aerosolized HPIV3/EboGP recipients exhibited high EBOV-specific IgG, IgA, and neutralizing antibody titers, which exceeded or equaled titers observed in liquid recipients. The HPIV3/EboGP vaccine induced an EBOV-specific cellular response that was greatest in the lungs and yielded polyfunctional CD8+ T cells, including a subset that expressed CD103 (αE integrin), and CD4+ T helper cells that were predominately type 1. The magnitude of the CD4+ T cell response was greater in aerosol vaccinees. The HPIV3/EboGP vaccine produced a more robust cell-mediated and humoral immune response than the systemic replicon vaccine. Moreover, 1 aerosol HPIV3/EboGP dose conferred 100% protection to macaques exposed to EBOV. Aerosol vaccination represents a useful and feasible vaccination mode that can be implemented with ease in a filovirus disease outbreak situation.
The G Protein α Subunit Has a Key Role in Determining the Specificity of Coupling to, but Not the Activation of, G Protein-gated Inwardly Rectifying K+ Channels (2000)

In neuronal and atrial tissue, G protein-gated inwardly rectifying K(+) channels (Kir3.x family) are responsible for mediating inhibitory postsynaptic potentials and slowing the heart rate. They are activated by Gbetagamma dimers released in response to the stimulation of receptors coupled to inhibitory G proteins of the G(i/o) family but not receptors coupled to the stimulatory G protein G(s). We have used biochemical, electrophysiological, and molecular biology techniques to examine this specificity of channel activation. In this study we have succeeded in reconstituting such specificity in an heterologous expression system stably expressing a cloned counterpart of the neuronal channel (Kir3.1 and Kir3.2A heteromultimers). The use of pertussis toxin-resistant G protein alpha subunits and chimeras between G(i1) and G(s) indicate a central role for the G protein alpha subunits in determining receptor specificity of coupling to, but not activation of, G protein-gated inwardly rectifying K(+) channels.
Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase. (1995)

Cyclin B/cdc2 is responsible both for driving cells into mitosis and for activating the ubiquitin-dependent degradation of mitotic cyclins near the end of mitosis, an event required for the completion of mitosis and entry into interphase of the next cell cycle. Previous work with cell-free extracts of rapidly dividing clam embryos has identified two specific components required for the ubiquitination of mitotic cyclins: E2-C, a cyclin-selective ubiquitin carrier protein that is constitutively active during the cell cycle, and E3-C, a cyclin-selective ubiquitin ligase that purifies as part of a approximately 1500-kDa complex, termed the cyclosome, and which is active only near the end of mitosis. Here, we have separated the cyclosome from its ultimate upstream activator, cdc2. The mitotic, active form of the cyclosome can be inactivated by incubation with a partially purified, endogenous okadaic acid-sensitive phosphatase; addition of cdc2 restores activity to the cyclosome after a lag that reproduces that seen previously in intact cells and in crude extracts. These results demonstrate that activity of cyclin-ubiquitin ligase is controlled by reversible phosphorylation of the cyclosome complex.
Association Between Glutathione S-Transferase P1, T1, and M1 Genetic Polymorphism and Survival of Patients With Metastatic Colorectal Cancer (2002)

The GSTP1 Ile(105)Val polymorphism is associated in a dose-dependent fashion with increased survival of patients with advanced colorectal cancer receiving 5-FU/oxaliplatin chemotherapy.
Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase (1994)

The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.
Chloride penetration and microstructure development of fly ash concrete (2012)

In the past decades, supplementary materials have been widely used in cement production. Fly ash (FA) with cheaper in price and with latent hydraulic properties, is one of the widely used supplementary materials. However, the addition of supplementary materials could influence the concrete properties. In general, the durability of concrete is associated with its transport properties. The transport properties, such as permeability, diffusivity and sorptivity are mainly resulted from the development of microstructure. In this study, the chloride migration coefficient measurement of FA concrete and the microstructural observation of cement paste blended with FA were carried out on the samples curing up to one year. Rapid Chloride Migration (RCM) test was used to determine the chloride migration coefficient of concrete. Meanwhile, Mercury Intrusion Porosimetry (MIP) method was conducted to obtain total porosity and pore size distribution of blended cement paste. Test results show that FA concrete has good resistance to chloride ion after the curing age of 28 days compared to ordinary Portland cement concrete. Although cement paste blended with FA has a higher total porosity, less capillary pore exist if compared to cement paste. Except the chloride binding capacity of FA hydrates, the difference in microstructure is probably one of the main reasons why FA concrete has a lower chloride migration coefficient.
Functional Expression of Exogenous Proteins in Mammalian Sensory Hair Cells Infected With Adenoviral Vectors (1999)

To understand the function of specific proteins in sensory hair cells, it is necessary to add or inactivate those proteins in a system where their physiological effects can be studied. Unfortunately, the usefulness of heterologous expression systems for the study of many hair cell proteins is limited by the inherent difficulty of reconstituting the hair cell's exquisite cytoarchitecture. Expression of exogenous proteins within hair cells themselves may provide an alternative approach. Because recombinant viruses were efficient vectors for gene delivery in other systems, we screened three viral vectors for their ability to express exogenous genes in hair cells of organotypic cultures from mouse auditory and vestibular organs. We observed no expression of the genes for beta-galactosidase or green fluorescent protein (GFP) with either herpes simplex virus or adeno-associated virus. On the other hand, we found robust expression of GFP in hair cells exposed to a recombinant, replication-deficient adenovirus that carried the gene for GFP driven by a cytomegalovirus promoter. Titers of 4 x 10(7) pfu/ml were sufficient for expression in 50% of the approximately 1,000 hair cells in the utricular epithelium; < 1% of the nonhair cells in the epithelium were GFP positive. Expression of GFP was evident as early as 12 h postinfection, was maximal at 4 days, and continued for at least 10 days. Over the first 36 h there was no evidence of toxicity. We recorded normal voltage-dependent and transduction currents from infected cells identified by GFP fluorescence. At longer times hair bundle integrity was compromised despite a cell body that appeared healthy. To assess the ability of adenovirus-mediated gene transfer to alter hair cell function we introduced the gene for the ion channel Kir2.1. We used an adenovirus vector encoding Kir2.1 fused to GFP under the control of an ecdysone promoter. Unlike the diffuse distribution within the cell body we observed with GFP, the ion channel-GFP fusion showed a pattern of fluorescence that was restricted to the cell membrane and a few extranuclear punctate regions. Patch-clamp recordings confirmed the expression of an inward rectifier with a conductance of 43 nS, over an order of magnitude larger than the endogenous inward rectifier. The zero-current potential in infected cells was shifted by -17 mV. These results demonstrate an efficient method for gene transfer into both vestibular and auditory hair cells in culture, which can be used to study the effects of gene products on hair cell function.
Nasal and pulmonary drug delivery systems (2000)

The respiratory route of administration has long been the medically desired drug delivery portal for the administration of topical anti-inflammatory drugs. These drugs are administered either to the lung, i.e., the lower respiratory system to treat asthma, or to the nasal cavity, i.e., the upper respiratory system to treat allergic rhinitis. This therapeutic focus dominates the drug delivery applications for the respiratory system. More recently, the respiratory system has provided a non-invasive method for the administration of biotherapeutics. And finally, formulation and device advancements have led to the consideration of the respiratory route for a number of other therapeutic applications where systemic delivery is desirable. All of these factors have resulted in the therapeutic patents that are discussed in this review.
Properties of Porous Silicon (1997)

Porous silicon has been the focus of much research activity in recent years, in view of its luminescence, which may enable light emitting devices to be integrated with silicon chips. This work comprises over 50 commissioned essays on the subject from scientists in Europe, America and Japan .
Issues in Publishing and the Internet in Medieval Islamic Studies (2002)

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Compounding for analgesia (2010)

The different methods of managing chronic pain is discussed. The advantages, methods, problems of administration of suppositories to manage pain are detailed.
Capacity-Achieving Polar Codes for Arbitrarily Permuted Parallel Channels (2012)

Channel coding over arbitrarily permuted parallel channels was first studied by Willems and coworkers. This paper introduces capacity-achieving polar coding schemes for arbitrarily permuted parallel channels where the component channels are memoryless, binary-input, and output-symmetric.
Recognizing Action at a Distance (2003)

Our goal is to recognize human actions at a distance, at resolutions where a whole person may be, say, 30 pix-els tall. We introduce a novel motion descriptor based on optical flow measurements in a spatio-temporal volume for each stabilized human figure, and an associated similarity measure to be used in a nearest-neighbor framework. Mak-ing use of noisy optical flow measurements is the key chal-lenge, which is addressed by treating optical flow not as precise pixel displacements, but rather as a spatial pattern of noisy measurements which are carefully smoothed and aggregated to form our spatio-temporal motion descriptor. To classify the action being performed by a human figure in a query sequence, we retrieve nearest neighbor(s) from a database of stored, annotated video sequences. We can also use these retrieved exemplars to transfer 2D/3D skeletons onto the figures in the query sequence, as well as two forms of data-based action synthesis “Do as I Do ” and “Do as I Say”. Results are demonstrated on ballet, tennis as well as football datasets. 1.
Electrostatic and Sterical Stabilization of TiO2 Dispersions (1995)

The influence of polyacrylic acid (MW 2000-10 000) on the stability of TiO2 dispersions was studied both in dil. suspensions (by light transmission) and in concd. dispersions (by rheol.). Polyacrylic acid in low concns. destabilizes TiO2 dispersions, but at higher concns., a stabilizing influence is found. In the high-concn. region, esp. stable dispersions can be obtained when electrostatic and steric stabilization act simultaneously. [on SciFinder (R)]
Multilayer Assemblies of Redox Polyelectrolytes (1997)

Polyelectrolyte multilayers containing electrochemically active viologen units have been constructed using the layer-by-layer deposition technique with poly(styrenesulfonate) and poly(butanylviologen) as polyanion and polycation, respectively. All redox active material is electrochemically addressable in multilayers made from these polymers. Cyclic voltammetry, ellipsometry, and UV−vis spectroscopy indicate a systematic dependence of the amount of material contained in these ultrathin films on the number of deposition cycles, although initial layers are significantly thinner. When the distance between a redox active layer and the electrode was varied by interposing non-electrochemically active layer pairs, it was determined that the material within the redox active layer was distributed over a distance of at least 2.5 layer pairs away from the nominal location of the redox active layer. This evidence for extensive interpenetration between layers was confirmed using variable-angle XPS, which revealed a 1:1 stoichiometry between charges on positive and negative polyelectrolytes in multilayers. No salt ions were detected in multilayers.
Development of the IIT research institute RF heating process for in situ oil shale/tar sand fuel extraction - an overview (1981)

The history and current status of development of IITRI's RF process for in situ oil shale/tar sand fuel extraction is described. A brief description of the salient features of IITRI's RF process is given, together with a review of past laboratory development activites. Activities within IITRI's current cooperative development program, jointly funded by government and industry, are also described, including oil shale fields tests, tar sand field tests, and supporting laboratory and analytical studies. 9 refs.
Nonholonomic Modeling of Needle Steering (2006)

As a flexible needle with a bevel tip is pushed through soft tissue, the asymmetry of the tip causes the needle to bend. We propose that, by using nonholonomic kinematics, control, and path planning, an appropriately designed needle can be steered through tissue to reach a specified 3D target. Such steering capability could enhance targeting accuracy and may improve outcomes for percutaneous therapies, facilitate research on therapy effectiveness, and eventually enable new minimally invasive techniques. In this paper, we consider a first step toward active needle steering: design and experimental validation of a nonholonomic model for steering flexible needles with bevel tips. The model generalizes the standard three degree-of-freedom (DOF) nonholonomic unicycle and bicycle models to 6 DOF using Lie group theory. Model parameters are fit using experimental data, acquired via a robotic device designed for the specific purpose of inserting and steering a flexible needle. The experiments quantitatively validate the bevel-tip needle steering model, enabling future research in flexible needle path planning, control, and simulation.
Nicotinic Receptors in Neurodegeneration (2013)

Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer's disease (AD), Parkinson's disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment.
Polar branch migration promoted by recA protein: effect of mismatched base pairs. (1982)

Escherichia coli recA protein makes joint molecules from single-stranded circular phage DNA (viral or plus strand) and homologous linear duplex DNA by a polar reaction that displaces the 5' end of the plus strand from the duplex molecule [Kahn, R., Cunningham, R. P., DasGupta, C. & Radding, C. M. (1981) Proc. Natl. Acad. Sci. USA 78, 4786-4790]. Growth of the heteroduplex joint, which results from strand exchange or branch migration, stopped at the borders of regions of nonhomologous DNA that were variously located 145, 630, or 1202 nucleotides from the end. Accumulation of migrating branches at heterologous borders demonstrates that their migration is not the result of random diffusion but is actively driven by recA protein. Growth of the heteroduplex joint was blocked even when a heterologous insertion was located in the single-stranded DNA, a case in which the flexible single-stranded region might conceivably fold out of the way under some condition. The recA protein did not make joint molecules from phage phi X174 and G4DNAs, which are 70% homologous, but did join phage fd and M13DNAs, which are 97% homologous. In the latter case, heteroduplex joints extended through regions containing isolated mismatched base pairs but stopped in a region where the fd and M13 sequences differ by an average of 1 base pair in 10. These results suggest that in genetic recombination the discrimination of perfect or near-perfect homology from a high degree of relatedness may be attributable in part to the mechanism by which recA protein promotes strand transfer.
Significance of non-level walking on transtibial prosthesis fitting with particular reference to the effects of anterior-posterior alignment. (2001)

Despite the fact that non-level walking is known to be important for prosthesis fitting, its clinical significance has not been investigated. In this study, the acceptable prosthesis alignment ranges of six subjects with transtibial amputation on level and non-level walking were determined and compared. With the aid of a recently developed alignment jig, prosthesis fitting was performed for each subject with varied anterior-posterior (AP) alignments. Conventional assessments and the subjects' comment were used to determine whether the alignment was acceptable or not. The results showed that the acceptable alignment range for non-level walking consistently fell within and was significantly smaller than that for level walking with p<0.05. It was evident that non-level walking is important for better approximation of optimum alignment and should be included in routine prosthesis fitting.