gebhart/patrepeval huggingface dataset:
Activation of Nrf2 Signaling As a Common Treatment of Neurodegenerative Diseases (2017)

The devastating age-dependent neurodegenerative disorders, including prevalent Alzheimer's (AD) and Parkinson's diseases (PD), as well as rare such as Huntington's chorea (HD) and Amyotrophic Lateral Sclerosis (ALS), affect millions of people worldwide.Their prevalence is projected to increase due to ageing of the population, with a corresponding increase in the associated socioeconomic impact.Currently, there is no disease-modifying therapy for any neurodegenerative disease.Symptomatic treatments are available for some conditions such as PD and HD, but the therapeutic benefits are transient and limited.Although the causative factors and clinical manifestations are distinct for each neurodegenerative disease, their molecular pathogeneses share common underlying factors, such as excessive levels of reactive oxygen species (ROS), largely due to mitochondrial impairment, neuroinflammation, and disturbances in protein homeostasis (proteostasis).This raises the exciting possibility for developing a universal treatment, targeting these common drivers of neurodegeneration.The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) orchestrates a major endogenous defense mechanism against oxidative and xenobiotic stress, and inflammation, and plays a role in the maintenance of mitochondrial function and cellular proteostasis, suggesting potential benefits of therapeutic targeting of Nrf2 to counteract neurodegeneration.Under stress condition(s), Nrf2 activates the transcriptional upregulation of a large network of cytoprotective genes, allowing adaptation and survival [1].The levels (and activity) of Nrf2 are tightly regulated through ubiquitination and proteasomal degradation mediated by several ubiquitin ligase systems, including Kelch-like ECHassociated protein 1 (Keap1)-Cullin3 (Cul3)/Rbx1, β-transducin repeats-containing protein (β-TrCP)-Cul1, and synoviolin (Hrd1) [2].Of these, Keap1 is the best-understood key negative regulator of Nrf2.Keap1 serves as a sensor for electrophiles and oxidants, which chemically modify specific cysteines in Keap1, resulting in conformational changes that protect Nrf2 from Keap1-directed degradation.As a
Comparison of culture with the polymerase chain reaction for detection of Ureaplasma urealyticum in endotracheal aspirates of preterm infants (1996)

Polymerase chain reaction (PCR) amplification of the urease genes of Ureaplasma urealyticum was compared with culture for detection of the organism in 100 endotracheal aspirates from 54 ventilated preterm infants. Ninety specimens gave negative results by both culture and PCR and three specimens gave positive results by both culture and PCR. Six specimens were negative by culture but positive by PCR. The one specimen positive by culture and negative by PCR was interpreted as a false-positive culture result. Overall agreement between results obtained by culture and PCR was 93%. PCR is a sensitive and reliable method for the detection of U. urealyticum in neonatal endotracheal secretions. Detection by PCR (1-2 days) is more rapid than culture (2-5 days) and this will be important if early therapeutic intervention is shown to be effective.
Analysis of an algorithm for distributed recognition and accountability (1993)

Computer and network systems are vulnerable to attacks. Abandoning the existing huge infrastructure of possibly-insecure computer and network systems is impossible, and replacing them by totally secure systems may not be feasible or cost effective. A common element in many attacks is that a single user will often attempt to intrude upon multiple resources throughout a network. Detecting the attack can become significantly easier by compiling and integrating evidence of such intrusion attempts across the network rather than attempting to assess the situation from the vantage point of only a single host. To solve this problem, we suggest an approach for distributed recognition and accountability (DRA), which consists of algorithms which “process”, at a central location, distributed and asynchronous “reports” generated by computers (or a subset thereof) throughout the network. Our highest-priority objectives are to observe ways by which an individual moves around in a network of computers, including changing user names to possibly hide his/her true identity, and to associate all activities of multiple instances of the same individual to the same networkwide user. We present the DRA algorithm and a sketch of its proof under an initial set of simplifying albeit realistic assumptions. Later, we relax these assumptions to accommodate pragmatic aspects such as missing or delayed “reports”, clock skew, tampered “reports”, etc. We believe that such algorithms will have widespread applications in the future, particularly in intrusion-detection systems.
Multiplex polymerase chain reaction. (1992)

The polymerase chain reaction (PCR) is a widely utilized assay for specifically amplifying small fragments of DNA. Multiplex PCR is the amplification of more than one DNA fragment per reaction and has many potential uses. When more than one primer set per reaction tube is utilized, the total number of tubes in any one experiment may be reduced, conserving expensive reagents and decreasing possible contamination. Multiplex PCR allows for an assay of the gene of interest and assures that the amplification process proceeds as expected with the use of a companion control genome primer set. Multiplex PCR is useful in assaying DNA extracted from samples of immunocompromised patients in which more than one infectious agent may be suspected such as simultaneous EBV and CMV detection. Multiplex PCR offers many advantages over single reaction PCR and has been found to be an useful adjunct in our laboratory.
Three-Dimensional Structure−Activity Relationships of Nonsteroidal Ligands in Complex with Androgen Receptor Ligand-Binding Domain (2005)

We studied the three-dimensional quantitative structure-activity relationships (3D QSAR) of 70 structurally and functionally diverse androgen receptor (AR) binding compounds using the comparative molecular similarity indices analysis (CoMSIA) method. The compound set contained 67 nonsteroidal analogues of flutamide, nilutamide, and bicalutamide whose binding mode to AR was unknown. Docking was used to identify the preferred binding modes for the nonsteroidal compounds within the AR ligand-binding pocket (LBP) and to generate the ligand alignment for the 3D QSAR analysis. The alignment produced a statistically significant and predictive model, validated by random group cross-validation and external test sets (q(2)(LOO) = 0.656, SDEP = 0.576, r(2) = 0.911, SEE = 0.293; q(2)(10) = 0.612, q(2)(5) = 0.571; pred-r(2) = 0.800). Additional model validation comes from the CoMSIA maps that were interpreted with respect to the LBP structure. The model takes into account and links the AR LBP structure, docked ligand structures, and the experimental binding activities. The results provide valuable information on intermolecular interactions between nonsteroidal ligands and the AR LBP.
Gene delivery into the central nervous system by nasal instillation in rats. (1995)

Replication-deficient adenoviruses have been used successfully to transfer foreign DNA into postmitotic cells. This article demonstrates that it is possible to transfer the Escherichia coli lacZ gene in vivo into the central nervous system structures of rats after nasal instillation of replication-defective adenoviral vector AdRSV beta gal. Mitral cells from the olfactory bulb, neurons from the anterior olfactory nucleus, locus coeruleus and area postrema expressed beta-galactosidase for at least 12 days. No cytopathic effect was observed in the CNS structures studied at the viral titer used (1-3 x 10(9) plaque-forming units (p.f.u.)). This method could be useful for the gene therapy of diseases affecting different CNS structures.
A Model of Cell Inactivation by Alpha-Particle Internal Emitters (1993)

Tumor-associated antibodies labeled with 131I and 90Y have been used in the treatment of malignant disease with some success. The use of alpha-particle-emitting radionuclides as radiolabels offers potential advantages over beta-particle sources. The short range in tissue (< 100 microns) and the high linear energy transfer associated with alpha-particle emitters will result in a more concentrated deposition of energy at the site of radionuclide decay. Thus, if radiolabeled antibodies can be bound to malignant cells specifically, a high differential cell killing can be achieved between the malignant and the normal cells. However, the energy deposition pattern will be strongly dependent upon the configuration of alpha-particle sources relative to the cells, and will consequently impact upon the dose-response characteristics. The purpose of this paper is to study distributions of energy deposition from alpha-particle-emitting radioimmunoconjugates distributed uniformly and nonuniformly around cells through theoretical modeling. Energy deposition spectra for cell nuclei are calculated and used to estimate the survival fraction by a simple biological model. We show that survival curves resulting from nonuniform distributions of alpha-particle-emitting radiolabeled antibodies can depart significantly from the classical exponential survival model applied to external alpha-particle beams. The survival curves may have initial slopes much steeper than those produced by a uniform distribution of sources, and they may also depart from linearity. Furthermore, the results of the modelling indicate how survival curves are dependent on the cell and radiolabel spacing. The results from our model compare reasonably well with published experimental data and can be used to facilitate the design and interpretation of radiobiological experiments.
IgA anti-tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy. (1999)

Tissue transglutaminase is a major autoantigen in coeliac disease. IgA (but not IgG) anti-tissue transglutaminase, especially when in high titre, is closely associated with coeliac disease, but low titres may not be disease specific. In this small pilot study, the established IgA anti-endomysial assay was the superior test.
Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation. (1990)

The effects of basic fibroblast growth factor (bFGF) on terminal differentiation of chondrocytes and cartilage-matrix calcification were investigated. Rabbit growth-plate chondrocytes maintained as a pelleted mass in a centrifuge tube produced an abundant proteoglycan matrix during the matrix-maturation stage, yielding a cartilage-like tissue. Thereafter, they terminally differentiated to hypertrophic chondrocytes which produced high levels of alkaline phosphatase. These cells induced extensive calcification of the matrix in the absence of additional phosphate (Kato, Y., Iwamoto, M., Koike, T., Suzuki, F., and Takano, Y. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 9552-9556). Addition of bFGF to the chondrocyte cultures abolished the increases in alkaline phosphatase activity, 45Ca deposition, and the calcium content. These effects were dose-dependent, reversible, and observed in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. The inhibitory effects could be observed only when chondrocytes were exposed to bFGF in a transition period between the matrix-maturation and hypertrophic stages. As chondrocytes differentiated to hypertrophic cells, bFGF became less effective in inhibiting the expression of the mineralization-related phenotypes. The present study also shows that although the rate of [35S]sulfate incorporation into large, chondroitin sulfate proteoglycan in the cell-matrix fraction is very high during the matrix-maturation stage, it abruptly decreases by 90% after terminal differentiation. Furthermore, the terminal differentiation-associated decrease in proteoglycan synthesis was delayed by bFGF. These results provide evidence that bFGF inhibits terminal differentiation of chondrocytes and calcification.
Adaptive Discriminative Generative Model and Its Applications (2004)

This paper presents an adaptive discriminative generative model that generalizes the conventional Fisher Linear Discriminant algorithm and renders a proper probabilistic interpretation. Within the context of object tracking, we aim to find a discriminative generative model that best separates the target from the background. We present a computationally efficient algorithm to constantly update this discriminative model as time progresses. While most tracking algorithms operate on the premise that the object appearance or ambient lighting condition does not significantly change as time progresses, our method adapts a discriminative generative model to reflect appearance variation of the target and background, thereby facilitating the tracking task in ever-changing environments. Numerous experiments show that our method is able to learn a discriminative generative model for tracking target objects undergoing large pose and lighting changes. 1
A functionally defined model for the M 2 proton channel of influenza A virus suggests a mechanism for its ion selectivity (1997)

The M2 protein from influenza A virus forms proton-selective channels that are essential to viral function and are the target of the drug amantadine. Cys scanning was used to generate a series of mutants with successive substitutions in the transmembrane segment of the protein, and the mutants were expressed in Xenopus laevis oocytes. The effect of the mutations on reversal potential, ion currents, and amantadine resistance were measured. Fourier analysis revealed a periodicity consistent with a four-stranded coiled coil or helical bundle. A three-dimensional model of this structure suggests a possible mechanism for the proton selectivity of the M2 channel of influenza virus.
Usage of the solar energy from the photovoltaic panels for the generation of electrical energy (1999)

This paper presents the analysis of a static conversion system for treatment of the solar energy from photovoltaic panels. This system is interconnected with the mains power supply, contributing to the generation of the electrical energy. The power structure is composed by a current-fed push-pull converter, a buck converter and a current inverter. The main features of the system are: simple control strategy, robustness, lower harmonic distortion of the current and natural isolation. The principle of operation, design procedure and experimental results are presented.
Characterization of molecular recognition of STAT3 SH2 domain inhibitors through molecular simulation (2010)

Signal transducer and activator of transcription 3 (STAT3) is an anti-cancer target protein due to its over-activation in tumor cells. The Tyr705-phosphorylated (pTyr) STAT3 binds to the pTyr-recognition site of its Src Homology 2 (SH2) domain of another STAT3 monomer to form a homo-dimer, which then causes cellular anti-apoptosis, proliferation, and tumor invasion. Recently, many STAT3 SH2 dimerization inhibitors have been discovered via both computational and experimental methods. To systematically assess their binding affinities and specificities, for eight representative inhibitors, we utilized molecular docking, molecular dynamics simulation, and ensuing energetic analysis to compare their binding characteristics. The inhibitors' binding free energies were calculated via MMPB(GB)SA, and the STAT3 SH2 binding "hot spots" were evaluated through binding energy decomposition and hydrogen bond (H-bond) distribution analysis. Several conclusions can be drawn: (1) the overall enthalpy-entropy compensation paradigm is preserved for the STAT3 SH2/ligand binding thermodynamics; (2) at one end of the binding spectrum, two compounds bind to SH2 due to their minimum entropic penalties that result from their relative rigidities and increased dynamics of SH2 upon their binding; at the other end of the binding spectrum, one compound shows a typical weak binder behavior due to its loose binding in the SH2's strongest enthalpy-contributing binding subsite; (3) hydrogen bonding seems a strong indicator to evaluate the SH2/ligand binding potency, which echoes a finding that CH/π non-classical H-bond is responsible for some pTyr peptides binding to their corresponding SH2 domains; (4) STAT3 SH2 domain possesses three binding "hot spots": pTyr705-binding pocket with polar residues and contributing the largest binding enthalpy (two-thirds); Leu706 subsite which is the most dynamic and hardest to target; a hydrophobic side pocket which is unique to STAT3 and very targetable, which may offer unique opportunity to design STAT3-specific inhibitors, particularly with fragment-based approach.
Determination of rumen microbial growth in vitro from32P-labelled phosphate incorporation (1977)

1. The extracellular phosphate pool in incubations of rumen fluid or washed cell suspensions of mixed rumen bacteria (WCS) was labelled with 32P. From the constant extracellular phosphate pool specific activity and the amount of radioactivity incorporated during incubation, the amount of P incorporated in the microbial fraction was calculated. From the value for nitrogen: P determined in microbial matter, the amount of N incorporated was calculated as a measure of microbial growth. 2. Incorporation of soluble non-protein-N in incubations devoid of substrate protein was 50 and 80% of the values obtained using the isotope method for rumen fluid and WCS respectively. It is suggested that results obtained using the former method reflect 'net growth' of micro-organisms which is the result of simultaneous growth and degradation. The isotope method measures 'total growth', as isotope incorporation is not affected by degradation of non-growing cells. 3. Incorporation of 32P in P-containing microbial components (mainly nucleic acids) was compared with net synthesis of these components in incubations of WCS. The results showed different specific rates of synthesis and degradation for all components studied. It is concluded that the composition of microbial matter changed during growth. 4. When N incorporation, calculated from results obtained using the isotope method in incubations with rumen fluid, was compared with the amount of carbohydrate substrate fermented and the type of fermentation, values between 18-3 and 44-6 g N incorporated/kg of organic matter fermented were obtained. Low values were associated with large proportions of the substrate being fermented to lactate and the use of glucose instead of disaccharides as substrate. Part of the variation could also be attributed to differences in incubation period, reflected in different proportions of polysaccharide formed. 5. The use of isotopes for determination of rumen microbial growth in vitro is critically discussed.
Identifying kinase dependency in cancer cells by integrating high-throughput drug screening and kinase inhibition data (2015)

Supplementary data are available at Bioinformatics online.
Design and growth of III&#x2013;V nanowire solar cell arrays on low cost substrates (2010)

State-of-the-art III-V multijunction cells have achieved a record efficiency of 42.8%, which has fueled great interest in the utility sector for large-scale deployment. However, III-V solar cells have thus far proven too expensive for widespread terrestrial applications due to the combined cost of substrates, growth processes, and materials. Here, we propose a novel III-V solar cell based on the epitaxial growth of AlGaAs/GaAs on Ge nanowires, pre-patterned on low cost substrates to achieve cost-effective, large-scale deployment. This approach is based on our recent discovery that the surface kinetics and epitaxial growth by MBE and MOCVD are dramatically altered when growing on nanostructures instead of planar surfaces. These growth kinetics enable uniform, single crystal growth of low-defect, lattice mismatched materials on nanostructures with high aspect ratios. We present the device design, TCAD simulation results, and experimental growth results for GaAs/Ge core-shell nanowires on silicon substrates. Finite-difference time-domain (FDTD) simulation results show that this GaAs/Ge nanowire array has reduced reflection and wider incident angle acceptance than its planar counterpart, and outperforms planar anti-reflective coatings under some conditions. GaAs is epitaxially grown on Ge nanowires via MBE and MOCVD. TEM measurements on the wires confirm that the GaAs/Ge core-shell structure is single crystal. Based on these results, we are in the process of fabricating GaAs/Ge nanowire solar cell arrays. We will present further characterization of these core-shell arrays as well as electrical measurements of solar cell devices.
Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes. (1990)

The following results were obtained in a long-term retrospective study including 250 patients with focal sclerosing glomerulonephritis: 1. The renal survival rate (RSR) was 90% at 5 years and 67% at 10 years, the average period of observation being 4.7 years. 2. Univariate analysis revealed that the following morphologic and clinical parameters are associated with an increased risk of terminal renal failure or death due to renal causes: a) Tubulointerstitial changes in the form of interstitial fibrosis, with or without acute renal failure; b) Advanced glomerular lesions; c) Advanced vascular alterations; d) Nephrotic syndrome present at the time of the biopsy; e) Elevated serum creatinine concentration at the time of the biopsy; f) Arterial hypertension at the time of the biopsy; g) Greater age at diagnosis; h) Male sex. 3. Multivariate survivorship analysis showed that tubulointerstitial changes and the presence of nephrotic syndrome at the time of biopsy are the only variables with significant independent predictive value for the outcome. Assessment of these factors thus allows the pathologist to make a relevant statement concerning the probable course and prognosis of the disease at the time of the diagnostic biopsy.
A video analysis framework for soft biometry security surveillance (2005)

We propose a distributed, multi-camera video analysis paradigm for aiport security surveillance. We propose to use a new class of biometry signatures, which are called soft biometry including a person's height, built, skin tone, color of shirts and trousers, motion pattern, trajectory history, etc., to ID and track errant passengers and suspicious events without having to shut down a whole terminal building and cancel multiple flights. The proposed research is to enable the reliable acquisition, maintenance, and correspondence of soft biometry signatures in a coordinated manner from a large number of video streams for security surveillance. The intellectual merit of the proposed research is to address three important video analysis problems in a distributed, multi-camera surveillance network: sensor network calibration, peer-to-peer sensor data fusion, and stationary-dynamic cooperative camera sensing.
Successful treatment of multiple sclerosis with magnetic fields. (1992)

The present communication concerns a 50 year-old woman with a 15 year history of chronic-progressive multiple sclerosis (MS) in whom extracranial application of picoTesla magnetic fields (MF) produced a dramatic and sustained improvement in disability. In contrast, administration of melatonin (3 mg, P.O.) produced in this patient a rapid exacerbation of disability which was reversed subsequently by treatment with MF. It is hypothesized that the therapeutic effects of picoTesla MF involve the mediation of the pineal gland which is known to act as a magnetosensor. The report demonstrates, for the first time, the remarkable efficacy of weak MF in the symptomatic treatment of chronic-progressive MS and underscores the pivotal role of the pineal gland in the pathophysiology of MS. If confirmed by a larger cohort of patients, extracranial application of picoTesla MF may prove as an extremely efficacious, nonpharmacological modality for the treatment of MS.