gebhart/patrepeval huggingface dataset:
Prospects for gene therapy in human prostate cancer (1998)

Prostate cancer is the most common neoplasm in men and a significant cause of mortality in affected patients. Despite significant advances, current methods of treatment are effective only in the absence of metastatic disease. Gene therapy offers a renewed hope of using the differential characteristics of normal and malignant tissue in constructing treatment strategies. Several clinical trials in prostate cancer gene therapy are currently under way, using immunomodulatory genes, anti-oncogenes, tumor suppressor genes and suicide genes. A continued understanding of the etiological mechanisms involved in the establishment and progression of prostate cancer, along with advances in gene therapy technology, should make gene therapy for prostate cancer therapeutically valuable in the future.
Noncoding Variants Functional Prioritization Methods Based on Predicted Regulatory Factor Binding Sites (2017)

Along with the rapid development of the high-throughout assays, more and more sample data and chromatin features would be conducive to improve the prediction accuracy of the deep convolution neural network for TFBSs identification. Meanwhile, getting more insights into the deep CNN framework itself has been proved useful for both the promotion on model performance and the development for more suitable design to sample data. Based on the feature values predicted by the deep CNN model, the prioritization model for functional noncoding variants would contribute to reveal the affection of gene mutation on the diseases.
Characterization of recombinant Bacillus megaterium cytochrome P-450 BM-3 and its two functional domains (1991)

Bacillus megaterium cytochrome P-450BM-3 and its two functional domains, the heme and flavin domains, have been purified and characterized using an Escherichia coli expression system. Recombinant P-450BM-3 behaves both spectrally and enzymatically the same as the enzyme produced from the natural host, B. megaterium, and another E. coli system recently described (Bouddupalli, S. S., Estabrook, R. W., and Peterson, J. A. (1990) J. Biol. Chem. 265, 4233-4239). Reduction of the flavins in P-450BM-3 domain with NADPH appears to be very similar to microsomal P-450 reductases where two reducing equivalents are consumed to fully reduce the FMN while the FAD is converted to the semiquinone in an one electron reduction. NADPH reduction of the heme occurs only in the presence of substrate suggesting, by analogy with the cytochrome P-450CAM system, a possible increase in iron redox potential of the heme upon substrate binding which facilitates electron transfer from the flavins to the heme. The flavin domain retains a high level of cytochrome c reductase activity and also reacts with NADPH to give a 3-electron reduced product. The heme domain retains the ability to bind substrate and generates the characteristic 450-nm absorption band upon reduction in the presence of CO. The heme domain has been crystallized and a preliminary set of x-ray diffraction data obtained.
Control Segment and User Performance (1978)

The concept validation phase (Phase I) of the Navstar GPS program will evaluate the performance of User receiving equipment and the Control Segment. The purpose of this paper is to describe how the Control Segment supports the User test program, and how Control Segment prediction errors in satellite ephemerides and atomic frequency standard behavior are propagated into User error. A summary of projected performance is also presented based on simulation results.
cGMP signalling in pre- and post-conditioning: the role of mitochondria (2007)

Much of cell death from ischaemia/reperfusion in heart and other tissues is generally thought to arise from mitochondrial permeability transition (MPT) in the first minutes of reperfusion. In ischaemic pre-conditioning, agonist binding to G(i) protein-coupled receptors prior to ischaemia triggers a signalling cascade that protects the heart from MPT. We believe that the cytosolic component of this trigger pathway terminates in activation of guanylyl cyclase resulting in increased production of cGMP and subsequent activation of protein kinase G (PKG). PKG phosphorylates a protein on the mitochondrial outer membrane (MOM), which then causes the mitochondrial K(ATP) channel (mitoK(ATP)) on the mitochondrial inner membrane to open, leading to increased production of reactive oxygen species (ROS) by the mitochondria. This implies that the protective signal is somehow transmitted from the MOM to its inner membrane. This is accomplished by a series of intermembrane signalling steps that includes protein kinase C (PKCepsilon) activation. The resulting ROS then activate a second PKC pool which, through another signal transduction pathway termed the mediator pathway, causes inhibition of MPT and reduction in cell death.
A soft voice activity detector based on a laplacian-gaussian model (2003)

A new voice activity detector (VAD) is developed in this paper. The VAD is derived by applying a Bayesian hypothesis test on decorrelated speech samples. The signal is first decorrelated using an orthogonal transformation, e.g., discrete cosine transform (DCT) or the adaptive Karhunen-Loeve transform (KLT). The distributions of clean speech and noise signals are assumed to be Laplacian and Gaussian, respectively, as investigated recently. In addition, a hidden Markov model (HMM) is employed with two states representing silence and speech. The proposed soft VAD estimates the probability of voice being active (VBA), recursively. To this end, first the a priori probability of VBA is estimated/predicted based on feedback information from the previous time instance. Then the predicted probability is combined/updated with the new observed signal to calculate the probability of VBA at the current time instance. The required parameters of both speech and noise signals are estimated, adaptively, by the maximum likelihood (ML) approach. The simulation results show that the proposed soft VAD that uses a Laplacian distribution model for speech signals outperforms the previous VAD that uses a Gaussian model.
Phenotypic Variation Resulting From a Deficiency of Epidermal Growth Factor Receptor in Mice Is Caused by Extensive Genetic Heterogeneity That Can Be Genetically and Molecularly Partitioned (2004)

The timing of lethality caused by homozygosity for a null allele of the epidermal growth factor receptor (Egfrtm1Mag) in mice is strongly dependent on genetic background. Initial attempts to genetically map background modifiers using Swiss-derived, outbred CD-1 mice were unsuccessful. To investigate the genetic architecture contributing to survival of Egfrtm1Mag homozygous embryos, the genetic variability segregating within the outbred population was partitioned by surveying viability of Egfrtm1Mag mutants using intercrosses between 129S6/SvEvTAC-Egfrtm1Mag and nine Swiss-derived, inbred strains: ALR/LtJ, ALS/LtJ, APN, APS, ICR/HaRos, NOD/LtJ, NON/LtJ, SJL/J, and SWR/J. The observations showed that these strains support varying levels of survival of Egfrtm1Mag homozygous embryos, suggesting that genetic heterogeneity within the CD-1 stock contributed to the original lack of Egfrtm1Mag modifier detection. Similar to the Swiss-derived intercrosses, nine congenic strains, derived from 129S6/SvEvTAC, AKR/J, APN, BALB/cJ, BTBR-T+ tf/tf, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ inbred backgrounds, also supported varying levels of survival of Egfrtm1Mag mutants. By intercrossing the congenic lines to create hybrid F1 embryos, different genetic backgrounds were found to have complementary modifiers. Analysis of the congenic lines argues against heterosis of outbred backgrounds contributing to Egfrtm1Mag phenotypic variability. A detailed analysis of the crosses suggests that modifiers function at three distinct stages of development. One class of modifiers supports survival of Egfrtm1Mag homozygous embryos to mid-gestation, another class supports development through the mid-gestation transition from yolk-sac to placental-derived nutrient sources, and a third class supports survival through later stages of gestation. Data from microarray analysis using RNA from wild-type and Egfrtm1Mag mutant placentas support the existence of extensive genetic heterogeneity and suggest that it can be molecularly partitioned. This method should be generally useful to partition heterogeneity contributing to other complex traits.
Improved Extensible Authentication Protocol Method for 3rd Generation Authentication and Key Agreement (EAP-AKA') (2009)

This specification defines a new EAP method, EAP-AKA', which is a small revision of the EAP-AKA (Extensible Authentication Protocol Method for 3rd Generation Authentication and Key Agreement) method. The change is a new key derivation function that binds the keys derived within the method to the name of the access network. The new key derivation mechanism has been defined in the 3rd Generation Partnership Project (3GPP). This specification allows its use in EAP in an interoperable manner. In addition, EAP-AKA' employs SHA-256 instead of SHA-1. This specification also updates RFC 4187, EAP-AKA, to prevent bidding down attacks from EAP-AKA'.
Colchicine Treatment for Recurrent Pericarditis (1998)

In light of new trial data that have accumulated in the past decade, we review the evidence for the efficacy and safety of colchicine for the prevention of recurrent episodes of pericarditis. Clinical and personal experience shows that colchicine may be an extremely promising adjunct to conventional treatment and may ultimately serve as the initial mode of treatment, especially in idiopathic cases.
Weed Response to Foliar Coapplications of Glyphosate and Zinc Sulfate (2009)

Field trials were conducted during 2006 and 2007 and a container study was performed twice in 2007 at the Dean Lee Research and Extension Center in Alexandria, LA to evaluate the interaction of glyphosate and zinc coapplied to selected weeds. Across all experiments, no differences in either visible weed control or weed fresh weight were detected among glyphosate formulations. In the field studies, weed control was greatest when glyphosate was applied alone, in which case control of barnyardgrass, browntop millet, and Palmer amaranth ranged between 93 and 95%. When glyphosate was coapplied with formulations of zinc, control of the aforementioned weed species was reduced to 39, 39, and 45%, respectively. Visual estimates of weed control in the container studies showed glyphosate performance to be the highest (82 to 98%) in the absence of zinc for control of barnyardgrass, browntop millet, johnsongrass, ivyleaf morningglory, and redroot pigweed. Across all weed species, control was reduced 43 to 59% when zinc was coapplied with glyphosate. Similar results were noted in reduction of weed fresh weights. Results indicate that glyphosate-based weed control is reduced when coapplied with the zinc products at their current use rates. Producers should be aware of this antagonism and these coapplications should not be recommended.
PHYSICAL MODELS AND DOSE FACTORS FOR USE IN INTERNAL DOSE ASSESSMENT (2003)

Internal dose assessment depends on the use of mathematical formulas for dose calculation and models of the human body and its organs. A simple, unified method for internal dose calculations is described, which brings together and simplifies concepts used in nuclear medicine and occupational internal dose systems previously described. Using the best current decay data and phantoms for internal dose calculations, dose factors for internal dose assessment are provided. Decay data for over 800 radionuclides from the data service at Brookhaven National Laboratory were combined with absorbed fraction data from a number of currently available mathematical whole body and organ models to provide the dose factors. This represents the first published update on nuclear medicine dose factors since MIRD Pamphlet No. 11 in 1975; in this paper, dose factors for many more nuclides are given (816 vs. 117 in MIRD 11), including some alpha emitters. New models are also employed, and dose factors for bone and marrow have been updated with recently suggested corrections. The good agreement of the new dose factors with previously published values for several of the models gives good confidence in their accuracy. This article gives an overview of the technical basis for these dose factors and some example tables of data, but the bulk of the data files will be distributed electronically. The use of an "electronic publishing" approach permits the publication of this kind of voluminous information in mainstream journals while facilitating rapid access and use without the need to purchase often expensive and bulky paper documents.
Networking Wireless Sensors (2005)

Wireless sensor networks promise an unprecedented fine-grained interface between the virtual and physical worlds. They are one of the most rapidly developing information technologies, with applications in a wide range of fields including industrial process control, security and surveillance, environmental sensing, and structural health monitoring. Originally published in 2005, this book provides a detailed and organized survey of the field. It shows how the core challenges of energy efficiency, robustness, and autonomy are addressed in these systems by networking techniques across multiple layers. The topics covered include network deployment, localization, time synchronization, wireless radio characteristics, medium-access, topology control, routing, data-centric techniques, and transport protocols. Ideal for researchers and designers seeking to create algorithms and protocols and engineers implementing integrated solutions, it also contains many exercises and can be used by graduate students taking courses in networks.
TNF-alpha in rheumatoid arthritis and prospects of anti-TNF therapy. (1993)

Our work has shown that TNF alpha is produced by cultured mononuclear cells from rheumatoid arthritis joints and appears to regulate the production of IL-1. Immunohistochemical examination has shown the presence of TNF alpha in the synovium, e.g. in the lining layer, some endothelial cells and most importantly, in the cells in the cartilage pannus junction. TNF receptors (both p55 and p75) have a similar distribution, thereby suggesting that TNF has the potential for autocrine and paracrine activity in the joint. The concept that TNF alpha is pathogenic in inflammatory arthritis has been validated by showing that neutralizing monoclonal anti-TNF antibodies significantly attenuate collagen-induced arthritis in mice. In preliminary trials in rheumatoid patients anti-TNF appears to have an impressive effect on indices of disease activity including C-reactive production and serum amyloid-A production. TNF alpha appears to be a relevant therapeutic target in rheumatoid disease.
Digital Channelizing Radio Frequency Receiver (2007)

HYPRES is developing a class of digital receivers featuring direct digitization at radio frequency (RF). Such a receiver consists of a wideband analog-to-digital converter (ADC) modulator and multiple digital channelizer units to extract different frequency bands-of-interest within the broad digitized spectrum. The single-bit oversampled data, from either a lowpass delta or bandpass delta-sigma modulator, are applied to one or more channelizers, each comprising digital in-phase and quadrature mixers and a pair of digital decimation filters. We perform channelization in two steps, the first at full ADC sampling clock frequency with rapid single flux quantum (RSFQ) digital circuits and the second at reduced (decimated) clock frequency with commercial field programmable gate array (FPGA) chips at room temperature. We have demonstrated lowpass and bandpass digital receivers by integrating an ADC modulator and a channelizer unit on the same chip at clock frequencies up to 20 GHz. These 1-cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> single-chip digital-RF receivers contain over 10,000 Josephson junctions. The channelizing receiver approach can be extended to include multiple ADC modulators and multiple channelizer units on a multi-chip module.
New type of disease causing mutations: the example of the composite exonic regulatory elements of splicing in CFTR exon 12 (2003)

The increase in genome scanning data, derived from clinical genetics practice, is producing a wealth of information on human sequence variability. The critical issue is to identify if a given nucleotide change results in a benign polymorphism or a disease-causing mutation. We have focused on one specific gene expression step, pre-mRNA processing, where we can functionally define the effect of nucleotide changes and in turn the patient's mutation can shed light on the basic pre mRNA splicing mechanisms. Our results show that several nucleotide changes in CFTR exon 12 induce a variable extent of exon skipping that leads to reduced levels of normal transcripts. This is the case in both natural mutations D565G and G576A (the latter having previously considered a neutral polymorphism) and several site-directed silent substitutions. We demonstrate here that this phenomenon is due to the interference with a new regulatory element that we have named composite exonic regulatory element of splicing (CERES). The effect of single nucleotide substitutions at CERES cannot be predicted by neither SR matrices nor enhancer identification. The recognition and characterization of splicing abnormalities, caused by exon sequence variations at CERES elements, may represent a frequent disease-causing mechanism that also relates to the phenotypic variability. Our results indicate that even the most benign looking polymorphism in an exon cannot be ignored as it may affect the splicing process. Hence, appropriate functional splicing assays should be included in genotype screenings to distinguish between polymorphisms and pathogenic mutations.
Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change (2003)

Protein kinase B (PKB/Akt) is a key regulator of cell growth, proliferation and metabolism. It possesses an N-terminal pleckstrin homology (PH) domain that interacts with equal affinity with the second messengers PtdIns(3,4,5)P3 and PtdIns(3,4)P2, generated through insulin and growth factor-mediated activation of phosphoinositide 3-kinase (PI3K). The binding of PKB to PtdIns(3,4,5)P3/PtdIns(3,4)P2 recruits PKB from the cytosol to the plasma membrane and is also thought to induce a conformational change that converts PKB into a substrate that can be activated by the phosphoinositide-dependent kinase 1 (PDK1). In this study we describe two high-resolution crystal structures of the PH domain of PKBalpha in a noncomplexed form and compare this to a new atomic resolution (0.98 A, where 1 A=0.1 nm) structure of the PH domain of PKBalpha complexed to Ins(1,3,4,5)P4, the head group of PtdIns(3,4,5)P3. Remarkably, in contrast to all other PH domains crystallized so far, our data suggest that binding of Ins(1,3,4,5)P4 to the PH domain of PKB, induces a large conformational change. This is characterized by marked changes in certain residues making up the phosphoinositide-binding site, formation of a short a-helix in variable loop 2, and a movement of variable loop 3 away from the lipid-binding site. Solution studies with CD also provided evidence of conformational changes taking place upon binding of Ins(1,3,4,5)P4 to the PH domain of PKB. Our data provides the first structural insight into the mechanism by which the interaction of PKB with PtdIns(3,4,5)P3/PtdIns(3,4)P2 induces conformational changes that could enable PKB to be activated by PDK1.
The vaccinia virus-stimulated mitogen-activated protein kinase (MAPK) pathway is required for virus multiplication (2004)

Early events play a decisive role in virus multiplication. We have shown previously that activation of MAPK/ERK1/2 (mitogen-activated protein kinase/extracellular-signal-regulated kinase 1/2) and protein kinase A are pivotal for vaccinia virus (VV) multiplication [de Magalhães, Andrade, Silva, Sousa, Ropert, Ferreira, Kroon, Gazzinelli and Bonjardim (2001) J. Biol. Chem. 276, 38353-38360]. In the present study, we show that VV infection provoked a sustained activation of both ERK1/2 and RSK2 (ribosomal S6 kinase 2). Our results also provide evidence that this pattern of kinase activation depends on virus multiplication and ongoing protein synthesis and is maintained independently of virus DNA synthesis. It is noteworthy that the VGF (VV growth factor), although involved, is not essential for prolonged ERK1/2 activation. Furthermore, our findings suggest that the VV-stimulated ERK1/2 activation also seems to require actin dynamics, microtubule polymerization and tyrosine kinase phosphorylation. The VV-stimulated pathway MEK/ERK1/2/RSK2 (where MEK stands for MAPK/ERK kinase) leads to phosphorylation of the ternary complex factor Elk-1 and expression of the early growth response (egr-1) gene, which kinetically paralleled the kinase activation. The recruitment of this pathway is biologically relevant, since its disruption caused a profound effect on viral thymidine kinase gene expression, viral DNA replication and VV multiplication. This pattern of sustained kinase activation after VV infection is unique. In addition, by connecting upstream signals generated at the cytoskeleton and by tyrosine kinase, the MEK/ERK1/2/RSK2 cascade seems to play a decisive role not only at early stages of the infection, i.e. post-penetration, but is also crucial to define the fate of virus progeny.
Individual Single-Walled Carbon Nanotubes as Nanoelectrodes for Electrochemistry (2004)

We demonstrate the use of individual single-walled carbon nanotubes (SWNTs) as nanoelectrodes for electrochemistry. SWNTs were contacted by nanolithography, and cyclic voltammetry was performed in aqueous solutions. Interestingly, metallic and semiconducting SWNTs yielded similar steady-state voltammetric curves. We clarify this behavior through a model that considers the electronic structure of the SWNTs. Interfacial electron transfer to the SWNTs is observed to be very fast but can nonetheless be resolved due to the nanometer critical dimension of SWNTs. These studies demonstrate the potential of using a SWNT as a model carbon nanoelectrode for electrochemistry.
Role of connective tissue growth factor in experimental radiation nephropathy in rats (2008)

Overexpression of CTGF may play an important role in the development and progression of glomerulosclerosis and tubulointerstitial fibrosis in radiation nephropathy.
Structural Requirements of Astrovirus Virus-Like Particles Assembled in Insect Cells (2004)

Expression of the complete ORF2 of human astrovirus serotype 1 (HAstV-1) in the baculovirus system led to the formation of virus-like particles (VLPs) of around 38 nm. The same kind of VLPs were also obtained either with the expression of a truncated form of ORF2 lacking the first 70 amino acids (aa), or with the same truncated form in which those 70 aa were replaced by the green fluorescent protein. All three kinds of VLPs were equally recognized by an anti-HAstV-1 polyclonal antibody and by two monoclonal antibodies (MAbs; 8E7 and 5B7), indicating a nonessential role of those amino acids neither in the capsid assembly nor in the antigen structure. A second type of structure consisting of 16-nm ring-like units was observed in all of the cases, mostly after disassembling the 38-nm VLPs through the addition of EDTA. The removal of the EDTA and the addition of Mg(2+) ions promoted the reassembly of the 38-nm VLPs. The nature of these 16-nm ring-like structures, capsomers or T = 1 VLPs, still remains unclear. Biochemical analysis revealed no differences between the 38-nm VLPs and the 16-nm structures, whereas antigenically, they shared the 8E7 MAb epitope but differed in the 5B7 MAb epitope, with the latter structures being more readily recognized.