gebhart/patrepeval huggingface dataset:
Cloning and nucleotide sequences of lux genes and characterization of luciferase of Xenorhabdus luminescens from a human wound (1991)

Xenorhabdus luminescens HW is the only known luminous bacterium isolated from a human (wound) source. A recombinant plasmid was constructed that contained the X. luminescens HW luxA and luxB genes, encoding the luciferase alpha and beta subunits, respectively, as well as luxC, luxD, and a portion of luxE. The nucleotide sequences of these lux genes, organized in the order luxCDABE, were determined, and overexpression of the cloned luciferase genes was achieved in Escherichia coli host cells. The cloned luciferase was indistinguishable from the wild-type enzyme in its in vitro bioluminescence kinetic properties. Contrary to an earlier report, our findings indicate that neither the specific activity nor the size of the alpha (362 amino acid residues, Mr 41,389) and beta (324 amino acid residues, Mr 37,112) subunits of the X. luminescens HW luciferase was unusual among known luminous bacterial systems. Significant sequence homologies of the alpha and beta subunits of the X. luminescens HW luciferase with those of other luminous bacteria were observed. However, the X. luminescens HW luciferase was unusual in the high stability of the 4a-hydroperoxyflavin intermediate and its sensitivity to aldehyde substrate inhibition.
Attempts to Mimic Docking Processes of the Immune System: Recognition-Induced Formation of Protein Multilayers (1993)

The assemblage of protein multilayers induced by molecular recognition, as seen, for example, in the immune cascade, has been mimicked by using streptavidin as a docking matrix. For these experiments, this protein matrix was organized on liposomes, monolayers at the air-water interface, and self-assembled layers on gold, all three containing biotin lipids. The docking of streptavidin to biotin at liposomal surfaces was confirmed by circular dichroism. Mixed double and triple layers of streptavidin, concanavalin A, antibody Fab fragments, and hormones are prepared at the air-water interface and on gold surfaces and were characterized by fluorescence microscopy and plasmon spectroscopy. With the use of biotin analogs that have lower binding constants it has been possible to achieve multiple formation and competitive replacement of the oriented protein assemblages.
Welding, Organizing, and Planting Organic Molecules on Substrate Surfaces—Promising Approaches towards Nanoarchitectonics from the Bottom up (2003)

Single molecule reactivity, self-assembly, and self-directed growth can be used to generate patterns on the nanometer scale. For example, molecular building blocks can be organized on substrate surfaces (see picture). New approaches that take advantage of single-molecule reactivity and self-organization, as well as stabilization of structures on substrate surfaces, are introduced.
Multiligand Endocytosis and Congenital Defects: Roles of Cubilin, Megalin and Amnionless (2007)

Cubilin and megalin are multiligand receptors that mediate uptake of extracellular ligands. Their function has extensively been studied in the kidney where they play a key role in vitamin B12 and vitamin D homeostasis. Amnionless is a plasma membrane protein that binds to cubilin in various epithelia; the interaction cubilin-amnionless in the gut is crucial for dietary vitamin B12 uptake. Studies in patients with gene defects in these receptors, and animal models with inactivated cubilin, megalin or amnionless suggest an important role in embryonic development and normal growth. In this review we will summarize recent data on the biological function of these receptors and focus on their implication in embryonic nutrition and central nervous system malformations. Keywords: Cubilin, megalin, amnionless, neural tube defects, endocytosis
Selecting Relevant Sensor Providers for Meeting "Your" Quality Information Needs (2011)

The accelerated, on-demand deployment of sensor networks raises the challenge of selecting the providers supplying the most "relevant" sensory information to a user's needs. This paper considers the spatial relevancy of information provided that accounts for the spatial gradations in the quality of the information desired and, specifically, considers: (a) selecting the minimum number of providers that cumulatively maximizes the information relevancy; and (b) considering a cost per provider, selecting the subset of providers that cumulatively maximizes the overall information relevancy subject to a budgetary constraint. The performance and robustness of the proposed solutions are studied both analytically and by simulation for a number of provider topologies.
Interleukin-6 in Sepsis and Capillary Leakage Syndrome (2011)

Bacterial sepsis is one of the most frequent and dreaded causes of death in intensive care units. According to the current understanding of sepsis, bacterial components activate innate immune responses via pattern-recognition receptors that stimulate signaling pathways, thereby leading to activation of NF-κB and the release of cytokines, alarming the organism and coordinating appropriate defense mechanisms. The resulting "cytokine storm" not only restricts bacterial invasion; it also harms the host by triggering a hemodynamic collapse with a drop in blood pressure, which could lead to death. One of the cytokines released during sepsis is interleukin-6 (IL-6). Originally described as a B-cell-stimulating factor, this cytokine has since been shown to have multiple additional functions. Interestingly, there is emerging evidence of IL-6 trans-signaling in the pathogenesis of sepsis. We review recent findings and discuss whether therapeutic interference with IL-6 trans-signaling may be beneficial in this important clinical scenario.
Using positional distribution to identify splicing elements and predict pre-mRNA processing defects in human genes (2011)

We present an intuitive strategy for predicting the effect of sequence variation on splicing. In contrast to transcriptional elements, splicing elements appear to be strongly position dependent. We demonstrated that exonic binding of the normally intronic splicing factor, U2AF65, inhibits splicing. Reasoning that the positional distribution of a splicing element is a signature of its function, we developed a method for organizing all possible sequence motifs into clusters based on the genomic profile of their positional distribution around splice sites. Binding sites for serine/arginine rich (SR) proteins tended to be exonic whereas heterogeneous ribonucleoprotein (hnRNP) recognition elements were mostly intronic. In addition to the known elements, novel motifs were returned and validated. This method was also predictive of splicing mutations. A mutation in a motif creates a new motif that sometimes has a similar distribution shape to the original motif and sometimes has a different distribution. We created an intraallelic distance measure to capture this property and found that mutations that created large intraallelic distances disrupted splicing in vivo whereas mutations with small distances did not alter splicing. Analyzing the dataset of human disease alleles revealed known splicing mutants to have high intraallelic distances and suggested that 22% of disease alleles that were originally classified as missense mutations may also affect splicing. This category together with mutations in the canonical splicing signals suggest that approximately one third of all disease-causing mutations alter pre-mRNA splicing.
Assembly and multiple gene expression of thermophilic enzymes in Escherichia coli for in vitro metabolic engineering (2014)

In vitro reconstitution of an artificial metabolic pathway is an emerging approach for the biocatalytic production of industrial chemicals. However, several enzymes have to be separately prepared (and purified) for the construction of an in vitro metabolic pathway, thereby limiting the practical applicability of this approach. In this study, genes encoding the nine thermophilic enzymes involved in a non-ATP-forming chimeric glycolytic pathway were assembled in an artificial operon and co-expressed in a single recombinant Escherichia coli strain. Gene expression levels of the thermophilic enzymes were controlled by their sequential order in the artificial operon. The specific activities of the recombinant enzymes in the cell-free extract of the multiple-gene-expression E. coli were 5.0-1,370 times higher than those in an enzyme cocktail prepared from a mixture of single-gene-expression strains, in each of which a single one of the nine thermophilic enzymes was overproduced. Heat treatment of a crude extract of the multiple-gene-expression cells led to the denaturation of indigenous proteins and one-step preparation of an in vitro synthetic pathway comprising only a limited number of thermotolerant enzymes. Coupling this in vitro pathway with other thermophilic enzymes including the H2 O-forming NADH oxidase or the malate/lactate dehydrogenase facilitated one-pot conversion of glucose to pyruvate or lactate, respectively.
Clock Tree synthesis for TSV-based 3D IC designs (2011)

For the cost-effective implementation of clock trees in through-silicon via (TSV)-based 3D IC designs, we propose core algorithms for 3D clock tree synthesis. For a given abstract tree topology, we propose DLE-3D ( d eferred l ayer e mbedding for 3D ICs), which optimally finds the embedding layers of tree nodes, so that the TSV cost required for a tree topology is minimized, and DME-3D ( d eferred m erge e mbedding for 3D ICs), which is an extended algorithm of the 2D merging segment, to minimize the total wirelength in 3D design space, with the consideration of the TSV effect on delay. In addition, when an abstract tree topology is not given, we propose NN-3D ( n earest n eighbor selection for 3D ICs), which constructs a (TSV and wirelength) cost-effective abstract tree topology for 3D ICs. Through experimentation, we have confirmed that the clock tree synthesis flow using the proposed algorithms is very effective, outperforming the existing 3D clock tree synthesis in terms of the number of TSVs, total wirelength, and clock power consumption.
Control system for an MRI compatible intracavitary ultrasound array for thermal treatment of prostate disease (2001)

A 16-channel ultrasound intracavitary array is currently being used in a clinical setting for localized hyperthermia treatment of prostate tumours. Currently, the individual power to each array element is adjusted based on the clinician's judgement of the temperature measured at the locations of invasive thermocouple probes. MRI-derived temperature measurements may be useful for a feedback control system that non-invasively regulates the temperature distribution by adjusting the power to the elements of the array. MRI has been shown to provide accurate, high resolution, non-invasive thermometry. A proportional-plus-integral, single-input, single-output controller was designed to evaluate the feasibility of MRI-derived temperature feedback with this applicator. Input parameters for the controller were determined by modelling the tissue response to the heating from the array. Ex vivo and in vivo experiments evaluated the ability of the MRI-based temperature feedback control system to achieve and maintain a target temperature for a sustained period similar to that of a clinical hyperthermia treatment. With the controller set to a reference temperature of 43°C and a rise time of 6min, the temperatures within the ex vivo tissue (n
Hyperkalemic periodic paralysis (1993)

We studied mutations of the adult voltage-gated skeletal muscle sodium channel gene in 12 families, from diverse ethnic backgrounds, with hyperkalemic periodic paralysis (HyperPP). We describe a novel procedure, using ligase chain reaction (LCR), to simultaneously identify two different point mutations (previously described) and one rare, apparently benign polymorphism that results in a nonconservative amino acid substitution. Three of 12 families showed the Met1592Val mutation, and six of 12 had the Thr704Met mutation. The mutation in three of the 12 families was not identified. In one of these three families, the disease was not linked to the adult voltage-gated sodium channel gene, suggesting the existence of a clinically similar but genetically distinct form of HyperPP. Genotype/phenotype correlations based on patient records and interviews in these families showed the variable and subjective nature of the illness, although the clinical distinctions between hyperkalemic periodic paralysis and paramyotonia congenita were reinforced by the molecular data.
Improved codes for space-time trellis-coded modulation (2000)

Space-time coded modulation has been shown to efficiently use transmit diversity to increase spectral efficiency. We propose new trellis codes found through systematic code search. These codes achieve the theoretically maximal diversity gain and improved coding gain compared to known codes.
Classes and Prediction of Cell-Penetrating Peptides (2010)

The classical view on how peptides enter cells has been changed due to the development in the research field of cell-penetrating peptides (CPPs). During the last 15 years, more than 100 peptide sequences have been published to enter cells and also to bring different biological cargoes with them. Here, we present an overview of CPPs, mainly trying to analyze their common properties yielding the prediction of their cell-penetrating properties. Furthermore, examples of recent research, ideas on classification and uptake mechanisms, as well as a summary of the therapeutic potential of CPPs are presented.
Generation of a triple‐gene knockout mammalian cell line using engineered zinc‐finger nucleases (2009)

Mammalian cells with multi-gene knockouts could be of considerable utility in research, drug discovery, and cell-based therapeutics. However, existing methods for targeted gene deletion require sequential rounds of homologous recombination and drug selection to isolate rare desired events--a process sufficiently laborious to limit application to individual loci. Here we present a solution to this problem. Firstly, we report the development of zinc-finger nucleases (ZFNs) targeted to cleave three independent genes with known null phenotypes. Mammalian cells exposed to each ZFN pair in turn resulted in the generation of cell lines harboring single, double, and triple gene knockouts, that is, the successful disruption of two, four, and six alleles. All three biallelic knockout events were obtained at frequencies of >1% without the use of selection, displayed the expected knockout phenotype(s), and harbored DNA mutations centered at the ZFN binding sites. These data demonstrate the utility of ZFNs in multi-locus genome engineering.
The Impacts of U.S. - China Trade on U.S. Manufacturing Unemployment (2012)

The U.S.-China economic ties have expanded over the past three decades with a substantial growth in both imports and exports. The total trade amount rose from only 2 billion in 1979 to over 457 billion in 2011. Although total trade increased over time, U.S. imports from China rose at a much higher rate than U.S. exports, and thus have caused a trade deficit since 1974, making China the U.S.’s biggest source of imports and second largest U.S. trading partner.
Modes of Fatty-Acid Desaturation in Cyanobacteria (1992)

The mode of desaturation of fatty acids in the membrane lipids of cyanobacteria was studied by analyzing the composition of fatty acids, the distribution of fatty acids at the sn position of the glycerol moiety, and the position of double bonds in the fatty acids. Cyanobacterial strains can be classified into four groups on the basis of the mode of desaturation of fatty acids. Cyanobacteria in Group 1 can introduce only one double bond at the Δ9 position of fatty acids at the sn-1 position. Cyanobacteria in Groups 2, 3 and 4 are characterized by a unique positional distribution of fatty acids; the C18 and C16 fatty acids are esterified, respectively, to the sn-1 and sn-2 positions of the glycerol moiety. In Group 2, the C18 acid is desaturated at the Δ9, Δ12, and Δ15 positions and the C16 acid is desaturated at the Δ9 and Δ12 positions; in Group 3, the C18 acid is desaturated at the Δ6, Δ9, and Δ12 positions; and in Group 4, the C18 acid is desaturated at the Δ6, Δ9, Δ12, and Δ15 positions. The C16 acid is not desaturated in Groups 3 and 4. Both unicellular and filamentous strains are distributed among all four groups.
A monolithic 480 Mb/s parallel AGG/decision/clock-recovery circuit in 1.2- mu m CMOS (1993)

A parallel architecture for high-data-rate AGC/decision/clock-recovery circuit, recovering digital NRZ data in optical-fiber receivers, is described. Improvement over traditional architecture in throughput is achieved through the use of parallel signal paths. An experimental prototype, fabricated in a 1.2- mu m double-poly double-metal n-well CMOS process, achieves a maximum bit rate of 480 Mb/s. The chip contains variable gain amplifiers, clock recovery, and demultiplexing circuits. It yields a BER of 10/sup -11/ with an 18 mV/sub p-p/ differential input signal. The power consumption is 900 mW from a single 5 V supply.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Myocardial tissue tagging with cardiovascular magnetic resonance (2009)

Cardiovascular magnetic resonance (CMR) is currently the gold standard for assessing both global and regional myocardial function. New tools for quantifying regional function have been recently developed to characterize early myocardial dysfunction in order to improve the identification and management of individuals at risk for heart failure. Of particular interest is CMR myocardial tagging, a non-invasive technique for assessing regional function that provides a detailed and comprehensive examination of intra-myocardial motion and deformation. Given the current advances in gradient technology, image reconstruction techniques, and data analysis algorithms, CMR myocardial tagging has become the reference modality for evaluating multidimensional strain evolution in the human heart. This review presents an in depth discussion on the current clinical applications of CMR myocardial tagging and the increasingly important role of this technique for assessing subclinical myocardial dysfunction in the setting of a wide variety of myocardial disease processes.
Diagnosis of Invasive Pneumococcal Disease among Children in Kenya with Enzyme-Linked Immunosorbent Assay for Immunoglobulin G Antibodies to Pneumococcal Surface Adhesin A (2005)

Diagnostic techniques for invasive pneumococcal disease (IPD) in children are insensitive and underestimate both the burden of disease and the cost-effectiveness of pneumococcal conjugate vaccination (PCV). Consequently, there is little demand for the highly effective PCV outside the United States and Europe. In Kenya, diagnosis of pneumococcal pneumonia in adults was achieved with a sensitivity of 0.70 and a specificity of 0.98 using enzyme-linked immunosorbent assays (ELISAs) of paired plasma samples for immunoglobulin G (IgG) to pneumococcal surface adhesin A (PsaA). We aimed to validate the same technique in children. We assayed paired blood samples from 98 children with IPD, 95 age-matched children with malaria/anemia, and 97 age-matched healthy controls by using an ELISA for anti-PsaA IgG. Sensitivity and specificity were determined in IPD patients and healthy controls. Specificity (0.97; 95% confidence interval [CI], 0.91 to 0.99) and sensitivity (0.42; 95% CI, 0.32 to 0.52) were optimized at a 2.7-fold rise in anti-PsaA antibody concentration. Sensitivity was improved to a maximum of 0.50 by restricting testing to children of <2 years old, by excluding IPD patients who were not sampled on the first day of presentation, and by incorporating high existing antibody concentrations in the analysis. Assay performance was independent of nasopharyngeal carriage of pneumococci at recruitment. This assay improves on existing diagnostic tools for IPD in children but would still leave over half of all cases undetected in epidemiological studies. Effective diagnosis of pneumococcal disease in children is urgently required but poorly served by existing technology.
Identification of Critical Residues in Bovine IFNAR-1 Responsible for Interferon Binding (2001)

Interferons have antiviral, antigrowth and immunomodulatory effects. The human type I interferons, IFN-alpha, IFN-beta, and IFN-omega, induce somewhat different cellular effects but act through a common receptor complex, IFNAR, composed of subunits IFNAR-1 and IFNAR-2. Human IFNAR-2 binds all type I IFNs but with lower affinity and different specificity than the IFNAR complex. Human IFNAR-1 has low intrinsic binding of human IFNs but strongly affects the affinity and differential ligand specificity of the IFNAR complex. Understanding IFNAR-1 interactions with the interferons is critical to elucidating the differential ligand specificity and activation by type I IFNs. However, studies of ligand interactions with human IFNAR-1 are compromised by its low affinity. The homologous bovine IFNAR-1 serendipitously binds human IFN-alphas with nanomolar affinity. Exploiting its strong binding of human IFN-alpha2, we have identified residues important for ligand binding. Mutagenesis of any of five aromatic residues of bovine IFNAR-1 caused strong decreases in ligand binding, whereas mutagenesis of proximal neutral or charged residues had smaller effects. These residues were mapped onto a homology model of IFNAR-1 to identify the ligand-binding face of IFNAR-1, which is consistent with previous structure/function studies of human IFNAR-1. The topology of IFNAR-1/IFN interactions appears novel when compared with previously studied cytokine receptors.
Modeling Modern Network Attacks and Countermeasures Using Attack Graphs (2009)

By accurately measuring risk for enterprise networks, attack graphs allow network defenders to understand the most critical threats and select the most effective countermeasures. This paper describes substantial enhancements to the NetSPA attack graph system required to model additional present-day threats (zero-day exploits and client-side attacks) and countermeasures (intrusion prevention systems, proxy firewalls, personal firewalls, and host-based vulnerability scans). Point-to-point reachability algorithms and structures were extensively redesigned to support "reverse" reachability computations and personal firewalls. Host-based vulnerability scans are imported and analyzed. Analysis of an operational network with 84 hosts demonstrates that client-side attacks pose a serious threat. Experiments on larger simulated networks demonstrated that NetSPA's previous excellent scaling is maintained. Less than two minutes are required to completely analyze a four-enclave simulated network with more than 40,000 hosts protected by personal firewalls.
Automation of Site Configuration Management (1997)

Although there are countless tools to track and manage the configuration of large numbers of Unix systems, there seems to be a lack of tools to manage the interaction and dependencies between systems. As our site has grown, many machines provide services that are required for the operation of other machines and applications. We have been unable to maintain accurate lists of services and servers, and even routine system upgrades have resulted in unexpected service outages. To address this problem, we are developing a system to automatically detect many of these service dependencies, and generate up to date server listings. In addition, it provides a general framework for indexing and accessing troubleshooting, operational, installation and a number of other types of documentation. The system also assists in verifying the configuration of systems being installed, and assists with the real time testing of services. Introduction As the number of Unix machines being supported gr...