gebhart/patrepeval huggingface dataset:
Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU (2017)

Phenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the importance of gut microbes in digestion, a genetically engineered microbe could potentially degrade some ingested phenylalanine from the diet prior to absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined conditions for freeze-drying and delivery of bacteria. Animals showed reduced blood phe within three to four days of treatment with pHENOMMenal probiotic, and blood phe concentrations remained significantly reduced (P < 0.0005) compared to untreated controls during the course of experiments. Although pHENOMMenal probiotic could be cultured from fecal samples at four months post treatment, it could no longer be cultivated from feces at eight months post treatment, indicating eventual loss of the microbe from the gut. Preliminary screens during experimentation found no immune response to AvPAL. Collectively these studies provide data for the use of a genetically engineered probiotic as a potential treatment for PKU.
LINCS: L-NAME (a NO synthase inhibitor) In the treatment of refractory Cardiogenic Shock A prospective randomized study (2003)

The results of the present study further support our previous observation that NO synthase inhibitors are beneficial in the treatment of patients with refractory cardiogenic shock.
Induction of centromeric activity in maize by suppressor of meiotic drive 1. (1996)

The Abnormal chromosome 10 (Ab10) in maize causes normally-quiescent blocks of heterochromatin called knobs to function as meiotic centromeres. Under these circumstances genetic markers associated with knobs exhibit meiotic drive, i.e., they are preferentially transmitted to progeny. Here we describe a mutation called suppressor of meiotic drive (smd1) that partially suppresses meiotic drive, and demonstrate that smd1 causes a quantitative reduction in the mobility of knobs on the meiotic spindle. We conclude that Smd1 encodes a product that is necessary for the activation of ectopic centromeres, and that meiotic drive occurs as a consequence of the resulting change in chromosome movement. As a genetic system, Ab10 offers a new and powerful approach for analyzing centromere/kinetochore function.
Sick Chaperones, Cellular Stress, and Disease (2005)

This review discusses the structure and function of molecular chaperones, with emphasis on their role in rescuing misfolded proteins. It also includes a discussion of the diseases in which abnormalities of these caretaker molecules or their molecular partners have been found.
Hardware-Efficient Autonomous Quantum Memory Protection (2013)

We propose to encode a quantum bit of information in a superposition of coherent states of an oscillator, with four different phases. Our encoding in a single cavity mode, together with a protection protocol, significantly reduces the error rate due to photon loss. This protection is ensured by an efficient quantum error correction scheme employing the nonlinearity provided by a single physical qubit coupled to the cavity. We describe in detail how to implement these operations in a circuit quantum electrodynamics system. This proposal directly addresses the task of building a hardware-efficient quantum memory and can lead to important shortcuts in quantum computing architectures.
Metal-Enhanced Fluorescence from Chromium Nanodeposits (2008)

Over the last several years, our laboratory has described in detail the favorable effects of fluorophores in close proximity to metallic nanoparticles. Metal nanoparticles comprised of gold, silver, copper, and zinc show enhanced fluorescence intensities and photostabilities for fluorophores positioned within 10 nm of the particles. In this paper we show that, in addition to these metals, chromium nanodeposits can also enhance the fluorescence of close proximity fluorophores, with probes such as fluorescein showing a greater than 8-fold enhancement. However, in contrast to gold, silver, and copper nanoparticles, fluorophores in close-proximity to chromium nanodeposits do not display reduced radiative lifetimes, suggesting that an enhanced electric field component (enhanced excitation rate) is the dominate mode of emission enhancement, similar to recent work by our laboratory for zinc nanoparticles. In addition, we also show the metal-sandwich geometries used in previous metal-enhanced fluorescence studies can give erroneous enhanced fluorescence readings, if care is not taken to normalize the excitation intensity/irradiance.
Prolyl Isomerase Cyclophilin A Regulation of Janus-Activated Kinase 2 and the Progression of Human Breast Cancer (2008)

The activation of the Janus-activated kinase 2 (Jak2) tyrosine kinase following ligand binding has remained incompletely characterized at the mechanistic level. We report that the peptidyl-prolyl isomerase (PPI) cyclophilin A (CypA), which is implicated in the regulation of protein conformation, is necessary for the prolactin (PRL)-induced activation of Jak2 and the progression of human breast cancer. A direct correlation was observed between the levels or activity of CypA and the extent of PRL-induced signaling and gene expression. Loss of PRLr-CypA binding, following treatment with the PPI inhibitor cyclosporine A (CsA), or overexpression of a dominant-negative PRLr mutant (P334A) resulted in a loss of PRLr/Jak2-mediated signaling. In vitro, CsA treatment of breast cancer cells inhibited their growth, motility, invasion, and soft agar colony formation. In vivo, CsA treatment of nude mice xenografted with breast cancer cells induced tumor necrosis and completely inhibited metastasis. These studies reveal that a CypA-mediated conformational change within the PRLr/Jak2 complex is required for PRL-induced transduction and function and indicate that the inhibition of prolyl isomerases may be a novel therapeutic strategy in the treatment of human breast cancer.
Nuclear Arms Control on the Korean Peninsula in a Changing World (1992)

The international arms control and disarmament scene today has many positive and negative features. On the positive side, first, the US and the former Soviet Union (or Commonwealth of Independent States) are engaged in a process of competitive disarmament. American and CIS strategic arms levels are still high, but the reductions have been significant and the arms race is being curbed. At the June 1992 Bush-Yeltsin summit both sides agreed to reduce their nuclear arms.’ Secondly, there is a new pattern in international relations: economic and domestic political difficulties of the powers are restraining their strategic behavior and the international arms race; more states are inward-looking now. Here internal weakness has pushed leaders to seek improvements in external relations. Economic compulsions led to Soviet capitulation in the international strategic sphere and this put an end to Soviet expansionism in all important regional spheres. The economic difficulties of the US economy have also dampened US military activities and furthermore, have reduced the political weight of the Pentagon in American decision-making. China’s enthusiasm for internal modernization, now ten years old, gives it an incentive to join the world market and moderate its external behavior. Overall, most countries are seeking
Reaction of lithium diphenylphosphonium di(methylide) with carbonic acid derivatives. A novel access to polyfunctional unsaturated esters and amides (1992)

Abstract The lithium diphenylphosphonium di(methylide) Ph 2 P(CH 2 ) 2 Li 1 readily attacks cyclic carbonates, carbamates, and thiocarbamates, resulting in “pseudo‐acylation” products, after a ring‐opening step. Thus, new stabilized ylides are prepared, which can be used in situ as carbonyl olefination reagents towards aldehydes. This procedure is a new one‐pot method for the synthesis of (E)‐vinylic esters and amides, bearing a free ω‐hydroxyl group. When a thiocarbamate is the initial substrate for 1 , a Michael‐type cyclization occurs, following the Wittig olefination, resulting in the one‐pot preparation of 7‐membered heterocycles.
A space-time model for reproducing rain field dynamics (2007)

The contribution presents a new model for assessing and characterizing rain field dynamics based on weather radar data.
Capture of Viral Particles in Soft X-Ray–Enhanced Corona Systems: Charge Distribution and Transport Characteristics (2004)

The charge distribution of airborne MS2 bacteriophage nanoparticles and the efficiency of electrical-mobility–based capture mechanisms with bipolar charging were studied. MS2 virions form large agglomerated particles in a suspension. The average charge on airborne MS2 virions can be as high as one unit charge (negatively charged). The application of both soft X-ray irradiation and alpha rays from a Po-210 bipolar charger was shown to not only reduce the average charge on MS2 virion particles but also partially fragment the larger MS2 virion agglomerates, thereby increasing the number of ultrafine MS2 virion particles. A cylindrical electrostatic precipitator with a mounted soft X-ray emitter was used to determine the effectiveness of electrical capture methods for virus particles. At low applied voltages, it was found that the capture efficiency of ultrafine virus particles can be increased by applying in situ soft X-ray irradiation with electrostatic precipitation. It has also been shown that in the presence of both a positive and negative corona, virus particles are readily captured with log removal values exceeding 4. The unit developed and demonstrated in this work is a compact, low-pressure drop system that can be readily mounted in ventilation ducts or air supply systems to remove ultrafine particles such as viruses.
Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. (1992)

Oral administration of myelin basic protein (MBP) is an effective way of suppressing experimental autoimmune encephalomyelitis (EAE). We have previously shown that such suppression is mediated by CD8+ T cells, which adoptively transfer protection and suppress immune responses in vitro. In the present study we have found that modulator cells from animals orally tolerized to MBP produce a suppressor factor upon stimulation with MBP in vitro that is specifically inhibited by anti-transforming growth factor beta (TGF-beta) neutralizing antibodies. No effect was observed with antibodies to gamma interferon, tumor necrosis factor alpha/beta, or indomethacin. In addition, the active form of the type 1 isoform of TGF-beta 1 (TGF-beta 1) can be directly demonstrated in the supernatants of cells from animals orally tolerized to MBP or ovalbumin after antigen stimulation in vitro. Antiserum specific for TGF-beta 1 administered in vivo abrogated the protective effect of oral tolerization to MBP in EAE. Furthermore, injection of anti-TGF-beta 1 serum to nontolerized EAE animals resulted in an increase in severity and duration of disease. These results suggest that immunomodulation of EAE induced by oral tolerization to MBP and natural recovery mechanisms use a common immunoregulatory pathway that is dependent on TGF-beta 1. Implications of such an association are of therapeutic relevance to human autoimmune diseases and may help to explain one of the mechanisms involved in the mediation of active suppression by T cells.
Human autoantibodies to carcinoembryonic antigen (CEA) induced by a vaccinia-CEA vaccine. (2000)

Carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human adenocarcinomas has been a target for cancer immunotherapy. Limited information is available regarding the ability of patients to mount an antibody response to this self-antigen following vaccination. Recombinant vaccinia viruses encoding full-length or internally deleted cDNAs for human CEA were used to vaccinate 32 patients with CEA-expressing adenocarcinomas, predominantly of colorectal origin. CEA-specific autoantibodies were induced by vaccination in 7 of 32 patients. None of the patients had CEA antibodies detected before vaccination. CEA specificity of the antibodies initially identified by ELISA was confirmed by competitive inhibition analysis as well as recognition of recombinant CEA produced in baculovirus-infected insect cell cultures and human cell cultures by Western blot. The CEA autoantibodies were predominantly IgG1, with a minority of patients also demonstrating IgM autoantibodies. CEA antibodies were of low titer and low avidity, based on competitive inhibition assays. These autoantibodies did not affect clinical serum CEA protein quantitation. Furthermore, elevated serum CEA levels commonly encountered in patients with advanced adenocarcinoma did not hinder detection of low avidity polyclonal CEA antibodies. CEA antibodies such as those induced in these pilot trials are projected to have modest antitumor activity. Thus, additional Phase I/II trials of recombinant vaccinia-CEA with alternative prime-boost approaches and/or augmentation strategies are warranted in an effort to enhance the frequency and avidity of CEA-specific autoantibodies and cytolytic T cells before Phase III trials.
HUMAN ALTERATION OF THE GLOBAL NITROGEN CYCLE: SOURCES AND CONSEQUENCES (1997)

Nitrogen is a key element controlling the species composition, diversity, dynamics, and functioning of many terrestrial, freshwater, and marine ecosystems. Many of the original plant species living in these ecosystems are adapted to, and function optimally in, soils and solutions with low levels of available nitrogen. The growth and dynamics of herbivore populations, and ultimately those of their predators, also are affected by N. Agriculture, combustion of fossil fuels, and other human activities have altered the global cycle of N substantially, generally increasing both the availability and the mobility of N over large regions of Earth. The mobility of N means that while most deliberate applications of N occur locally, their influence spreads regionally and even globally. Moreover, many of the mobile forms of N themselves have environmental consequences. Although most nitrogen inputs serve human needs such as agricultural production, their environmental consequences are serious and long term. Based on our review of available scientific evidence, we are certain that human alterations of the nitrogen cycle have: approximately doubled the rate of nitrogen input into the terrestrial nitrogen cycle, with these rates still increasing; increased concentrations of the potent greenhouse gas N2O globally, and increased concentrations of other oxides of nitrogen that drive the formation of photochemical smog over large regions of Earth; caused losses of soil nutrients, such as calcium and potassium, that are essential for the long-term maintenance of soil fertility; contributed substantially to the acidification of soils, streams, and lakes in several regions; and greatly increased the transfer of nitrogen through rivers to estuaries and coastal oceans. In addition, based on our review of available scientific evidence we are confident that human alterations of the nitrogen cycle have: increased the quantity of organic carbon stored within terrestrial ecosystems; accelerated losses of biological diversity, especially losses of plants adapted to efficient use of nitrogen, and losses of the animals and microorganisms that depend on them; and caused changes in the composition and functioning of estuarine and nearshore ecosystems, and contributed to long-term declines in coastal marine fisheries.
Quenching of Fluorescence in Europium β-Diketone Chelate Solutions and Its Application to Display Devices (1979)

The quenching of ultraviolet-stimulated fluorescence by voltage application was investigated using sandwich-type cells prepared with DMF (dimethylformamide) solutions of pyrrolidinium salts of europium tetrakis benzoyltrifluoroacetonate. The red fluorescence is quenched when a negative voltage is applied to a transparent electrode exposed to ultraviolet irradiation. Quenching of the fluorescence is also observed with some delay after applying a voltage with reverse polarity. The quenching mechanism is discussed using a simple model in which the chelate molecules diffuse with the reduced nonradiative divalent europium ions from the negative electrode. This phenomenon can be applied to display devices; the contrast ratio, the response and recovery times, and a method for reducing the recovery time are described.
Random Hole Display: A non-uniform barrier autostereoscopic display (2009)

A novel design for an autostereoscopic (AS) display is demonstrated featuring a randomized hole distribution parallax barrier. The Random Hole Display (RHD) design eliminates the repeating zones found in regular barrier and lenticular autostereoscopic displays, enabling multiple simultaneous viewers in arbitrary locations. The primary task of a multi-user AS display is to deliver the correct and unique view to each eye of each observer. If multiple viewers see the same pixels behind the barrier, then a conflict occurs. Regular barrier displays have no conflicts between views for many viewer positions, but have significant, localized conflicts at regular intervals across the viewing area and when viewed at different distances from the display. By randomizing the barrier pattern the RHD exhibits a small amount of conflict between viewers, distributed across the display, in all situations. Yet it never exhibits the overwhelming conflicts between multiple views that are inherent in conventional AS displays. With knowledge of user locations, the RHD presents the proper stereoscopic view to one or more viewers. It further mitigates viewing conflicts by allowing display pixels that are seen by more than one viewer to remain active by optionally blending the similar colors of desired views. Interference between views for random hole barriers and for a conventional regular barrier pattern are simulated. Results from a proof-of-concept Random Hole Display are presented.
Early Lung Cancer Action Project: overall design and findings from baseline screening (1999)

Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage. Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.
ACNUC: a nucleic acid sequence data base and analysis system (1984)

Structured as a data base and associated with data analysis tools, ACNUC allows both on-line access to a central computer and local exploitation of published nucleotide sequences. Its data retrieval capabilities seem to be presently the most powerful available.
Mice are actively immunized after passive monoclonal antibody prophylaxis and ricin toxin challenge. (1992)

Mice passively immunized by a protective, anti-ricin A-chain monoclonal antibody, then challenged intravenously with ricin, were protected from a subsequent ricin challenge, and were actively immunized. Two significant advantages accrued from this experiment: the monoclonal antibody neutralized the toxicity of the ricin immunogen, and active immunization was achieved with very low antigen load (approximately 0.5 microgram/mouse). We ruled out the possibility that residual monoclonal antibody provided the protection by using three independent criteria. There was significant (four orders of magnitude) enhancement of the immune response in the presence of the monoclonal antibody; control immunizations of mice with ricin A-chain, ricin B-chain or either chain with the monoclonal antibody did not induce active immunity; and the active immunization could not be replicated when protective goat polyclonal antibody was substituted for the monoclonal antibody. Because high titres were achieved rapidly without any adjuvant, we are currently investigating haptenized ricin to determine if anti-hapten monoclonal antibodies can be produced by this refined procedure.
In vitro release characteristics and cellular uptake of poly(D,L-lactic-co-glycolic acid) nanoparticles for topical delivery of antisense oligodeoxynucleotides (2011)

The efficacy of antisense oligodeoxynucleotides (AsODNs) is compromised by their poor stability in biological fluids and the inefficient cellular uptake due to their size and negative charge. Since chemical modifications of these molecules have resulted in a number of non-antisense activities, incorporation into particulate delivery systems has offered a promising alternative. The aim of this study was to evaluate various poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles for AsODN entrapment and delivery. PLGA nanoparticles were prepared using the double emulsion solvent evaporation method. The influence of formulation parameters such as PLGA concentration and volume ratio of internal aqueous phase volume (Va1) to organic phase volume (Vo) to external aqueous phase volume (Va2) on particle size, polydispersity index (PDI) and zeta potential (ZP) was investigated using a full factorial study. The particle size increased with increasing PLGA concentrations and volume ratios, with an interaction detectable between the two factors. AsODN entrapment efficiencies ranged between 49.97% and 54.95% with no significant difference between various formulations. By fitting the in vitro release profiles to a dual first order release model it was shown that the AsODN release occurred via two processes: a diffusion controlled process in the early phase (25 to 32% within one day) and a PLGA degradation process in the latter (39 to 70% after 14 days). Cellular uptake studies using primary corneal epithelial cells suggested active transport of nanoparticles via endocytosis. PLGA nanoparticles therefore show potential to successfully entrap AsODNs, transport them into cells and release them over time due to polymer erosion.
Phosphorothioate Oligonucleotide-Directed Triple Helix Formation (1994)

Phosphorothioate oligodeoxyribonucleotides were tested for their ability to recognize double-helical DNA in two distinct triple helix motifs. Purine-rich oligonucleotides containing a diastereomeric mixture of phosphorothioate or stereoregular (all RP) phosphorothioate linkages are shown to form triple-helical complexes with affinities similar to those of the corresponding natural phosphodiester oligonucleotides. In contrast, pyrimidine-rich phosphorothioate oligonucleotides containing a mixture of diastereomeric or stereoregular (all RP) linkages do not bind to double-helical DNA with measurable affinity. These observations have implications for triple helix structure and for biological applications.
Apolipoprotein E Polymorphism (2000)

These data give evidence that patients with the apoE 3/3 genotype have a better chance of recovery after cardiopulmonary resuscitation than do patients with apoE genotypes other than 3/3.