gebhart/patrepeval huggingface dataset:
Cross-Term Forwarding for Systems With Time Delay (2009)

This paper presents a Lyapunov-based control design method for nonlinear systems with time delay. The key step is construction of a composite Lyapunov functional <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> for a stable cascade. This functional consists of Lyapunov functionals for the subsystems and a cross-term defined by an infinite integral. The ldquo <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">g</sub> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> -typerdquo control law is then employed to achieve global asymptotic stability. The design procedure can be applied recursively to stabilize complex feedforward structures. When applied to a linear cascade, it gives a formula for the control law even if some parts of the system can only be stabilized through channels with multiple non-commensurate or distributed delays.
A Theoretical Treatment of PA Power Optimization in Clipped MIMO-OFDM Systems (2009)

This work presents a theoretical framework for determining the optimal clipping level for a multiple input multiple output (MIMO) orthogonal frequency division multiplexing (OFDM) system. We start by modeling of the clipping noise, and propose a maximum likelihood (ML) receiver for the resulting signal. The bit error rate (BER) for this ML receiver is then derived for MIMO spatial multiplexing, space time coding, and cyclic delay diversity schemes. A search through the tradeoff space between the BER performance penalty and power amplifier (PA) power consumption advantage reveals optimum clipping levels of the system. Using an IEEE 802.11n like system, we show that the optimum clipping as predicted by this approach can improve PA power efficiency as much as 70%.
Cascade multilevel static synchronous compensator configuration for wind farms (2011)

Modulation and control of a cascade multilevel static synchronous compensator (STATCOM) configuration to improve the quality of voltage generated by wind power systems are presented. The proposed STATCOM configuration needs only four dc-link capacitors and 24 switches to synthesise nine-level operation. In addition to that, switching losses are further reduced by splitting the voltage source inverter of the STATCOM into two units called the ‘bulk inverter’ and the ‘conditioning inverter’. The high-power bulk inverter is operated at low frequency whereas the low-power conditioning inverter is operated at high frequency to suppress harmonics produced by the bulk inverter. Fluctuations at the point of common coupling voltage, caused by sudden wind changes, are suppressed by controlling reactive power of the STATCOM. Simulation and experimental results are presented to verify the efficacy of the proposed modulation and control techniques used in the STATCOM.
Correlation ofPseudomonas aeruginosavirulence factors from clinical and environmental isolates with pathogenicity in the neutropenic mouse (1997)

The potential pathogenicity of a microorganism is a major concern for Health Canada evaluators, who will be processing new biotechnology products under the Canadian Environmental Protection Act. Potential pathogenicity is generally predicted by the results of animal pathogenicity studies. In an attempt to define surrogate data for an animal model, this study was initiated. Pseudomonas aeruginosa isolates from clinical and environmental sources were screened for their pilus type, serotype, lipopolysaccharide type, ability to evade host responses, and production of toxin A, exoenzyme S, elastase, phospholipase C, and total protease. The 50% lethal dose (LD50) of the same isolates was determined in the neutropenic mouse model of infection. An attempted correlation was drawn between each (or combinations) of the virulence determinants and the LD50. Stepwise linear regression showed that the presence of high levels of exoenzyme S in association with elastase or phospholipase C, or to a minor extent toxin A, was correlated with low numbers of bacteria required to elicit an LD50. No correlation between any of the other factors examined and virulence was detected. The data suggest that an in vitro high level of exoenzyme S production could be used as surrogate information for neutropenic mouse modelling; however, the levels of all of the extracellular enzymes should be considered when making such an assessment.
Differences in Intracellular DNA Ligation After Microinjection and Transfection (1984)

An uninterrupted avian sarcoma viral genome terminated by viral long terminal repeat sequences was cloned into a pBR322 plasmid. After introduction into a cultured avian cell, transcription of either the circular plasmid molecule or one linearized within the pBR322 sequences could initiate and terminate at long terminal repeat sequences, yielding full-sized viral RNA. A plasmid DNA molecule linearized by cleavage within the viral pol gene, on the other hand, would have to undergo ligation to yield full-sized viral RNA. Microinjection of each of these three types of DNA into the nuclei of quail cells promoted the release of similar virus titers, indicating that the plasmid DNA cleaved within the viral pol gene had been efficiently and accurately ligated. When plasmid DNA was transfected into quail cells, circular and pBR322-cleaved molecules directed the synthesis of similar virus titers, indicating that they were similarly taken up and utilized by the cells. Compared with these results, plasmid DNA cleaved within the pol gene was reduced in activity over 95% after transfection. This reduction did not result from inefficient ligation but from the generation of mutations (of limited size) during ligation of the transfected molecules. Mutations were not observed after microinjection even into the cytoplasm. Consistent with these findings, transfected DNA termini were found to be joined regardless of their structure, whereas ligation after microinjection required that single-stranded protruding DNA termini be complementary.
Thin-film stack based integrated GRIN coupler with aberration-free focusing and super-high NA for efficient fiber-to-nanophotonic-chip coupling (2010)

Nanophotonic chip coupling using an optical thin-film stack forming a micro graded-refractive-index (GRIN) lens with a super-high numerical aperture (NA) that is highly compact (tens of micron long) and can be directly integrated is presented. We explore the lens' integration on the surface of Silicon-On-Insulator (SOI) platform with an asymmetric GRIN profile. We show that to achieve high efficiency for optical coupling between an optical fiber and a nanophotonic waveguide with a sub-wavelength (lambda/n) beam size, conventional asymmetric parabolic GRIN profile is no longer adequate due to the super-high NA needed (>3.1), which results in severe spatial beam aberration at the focal plane. We present an efficient algorithm to computationally generate the ideal GRIN profile that is completely aberration free even at super-high NA, which improves the coupling efficiency from ~66% (parabolic case) to ~95%. A design example involving an optical thin-film stack using an improved dual-material approach is given. The performance of the thin-film stack is analyzed. This thin-film stack based GRIN lens is shown to be high in coupling efficiency, wavelength insensitive and compatible with standard thin-film process.
Children with Infantile Neuronal Ceroid Lipofuscinosis Have an Increased Risk of Hypothermia and Bradycardia During Anesthesia (2009)

We report that patients with INCL have lower baseline body temperature and during general anesthesia, despite rewarming interventions, are at increased risk for hypothermia and bradycardia. This suggests a previously unknown INCL phenotype, impaired thermoregulation. Therefore, when anesthetizing these children, careful monitoring and routine use of warming interventions are warranted.
Rescue of enzyme deficiency in embryonic diaphragm in a mouse model of metabolic myopathy: Pompe disease (2004)

Several human genetic diseases that affect striated muscle have been modeled by creating knockout mouse strains. However, many of these are perinatal lethal mutations that result in death from respiratory distress within hours after birth. As the diaphragm muscle does not contract until birth, the sudden increase in diaphragm activity creates permanent injury to the muscle causing it to fail to meet respiratory demands. Therefore, the impact of these mutations remains hidden throughout embryonic development and early death prevents investigators from performing detailed studies of other striated muscle groups past the neonatal stage. Glycogen storage disease type II (GSDII), caused by a deficiency in acid alpha-glucosidase (GAA), leads to lysosomal accumulation of glycogen in all cell types and abnormal myofibrillogenesis in striated muscle. Contractile function of the diaphragm muscle is severely affected in both infantile-onset and late-onset individuals, with death often resulting from respiratory failure. The knockout mouse model of GSDII survives well into adulthood despite the gradual weakening of all striated muscle groups. Using this model, we investigated the delivery of recombinant adeno-associated virus (rAAV) vectors encoding the human GAA cDNA to the developing embryo. Results indicate specific high-level transduction of diaphragm tissue, leading to activity levels up to 10-fold higher than normal and restoration of normal contractile function. Up to an estimated 50 vector copies per diploid genome were quantified in treated diaphragms. Histological glycogen staining of treated diaphragms revealed prevention of lysosomal glycogen accumulation in almost all fibers when compared with untreated controls. This method could be employed with disease models where specific rescue of the diaphragm would allow for increased survival and thus further investigation into the impact of the gene deletion on other striated muscle groups.
Future GOES-R global ground receivers (2006)

The Aerospace Corporation has developed an end-to-end testbed to demonstrate a wide range of modern modulation and coding alternatives for future broadcast by the GOES-R Global Rebroadcast (GRB) system. In particular, this paper describes the development of a compact, low cost, flexible GRB digital receiver that was designed, implemented, fabricated, and tested as part of the development. This receiver demonstrates a 10-fold increase in data rate compared to the rate achievable by the current GOES generation, without a major impact on either cost or size. The digital receiver is integrated on a single PCI card with an FPGA device, and analog-to-digital converters. It supports a wide range of modulations (including 8-PSK and 16-QAM) and turbo coding. With appropriate FPGA firmware and software changes, it can also be configured to receive the current (legacy) GOES signals. The receiver has been validated by sending large image files over a high-fidelity satellite channel emulator, including a space-qualified power amplifier and a white noise source. The receiver is a key component of a future GOES-R weather receiver system (also called user terminal) that includes the antenna, low-noise amplifier, downconverter, filters, digital receiver, and receiver system software. This work describes this receiver proof of concept and its application to providing a very credible estimate of the impact of using modern modulation and coding techniques in the future GOES-R system.
Preparation of New Bioactive Hybrid Bone Cements Containing Bis‐GMA Derivatives as a Prepolymer (2006)

Abstract Summary: Novel organic‐inorganic hybrid bioactive bone cements containing bisphenol‐A‐glycidyl methacrylate (Bis‐GMA) derivatives and a bioactive inorganic filler were prepared for orthopedic applications. The Bis‐GMA derivatives, such as 3MA and a 3MA mixture (3MA mix), were synthesized by blocking one or two of the hydroxyl groups of the Bis‐GMA so as to use it as a prepolymer. Four organic prepolymers, such as Bis‐GMA, 3MA, 3MA 50 and 3MA mix, and an inorganic filler, AW‐GC, were used for the preparation of the bioactive bone cements and their characteristics were evaluated. As compared with the Bis‐GMA control, the new bioactive bone cements containing the Bis‐GMA derivatives exhibited appropriate curing times, low polymerization shrinkage, low water absorption and solubility as well as high mechanical properties. In particular, the bioactive bone cement containing 3MA mix and AW‐GC had higher bending and compressive strengths than the Bis‐GMA one. Curing time and polymerization shrinkage on various prepolymers of bioactive bone cements. magnified image Curing time and polymerization shrinkage on various prepolymers of bioactive bone cements.
Remission for Loss of Odontogenic Potential in a New Micromilieu In Vitro (2016)

During embryonic organogenesis, the odontogenic potential resides in dental mesenchyme from the bud stage until birth. Mouse dental mesenchymal cells (mDMCs) isolated from the inductive dental mesenchyme of developing molars are frequently used in the context of tooth development and regeneration. We wondered if and how the odontogenic potential could be retained when mDMCs were cultured in vitro. In the present study, we undertook to test the odontogenic potential of cultured mDMCs and attempted to maintain the potential during culturing. We found that cultured mDMCs could retain the odontogenic potential for 24 h with a ratio of 60% for tooth formation, but mDMCs were incapable of supporting tooth formation after more than 24 h in culture. This loss of odontogenic potential was accompanied by widespread transcriptomic alteration and, specifically, the downregulation of some dental mesenchyme-specific genes, such as Pax9, Msx1, and Pdgfrα. To prolong the odontogenic potential of mDMCs in vitro, we then cultured mDMCs in a serum-free medium with Knockout Serum Replacement (KSR) and growth factors (fibroblastic growth factor 2 and epidermal growth factor). In this new micromilieu, mDMCs could maintain the odontogenic potential for 48 h with tooth formation ratio of 50%. Moreover, mDMCs cultured in KSR-supplemented medium gave rise to tooth-like structures when recombined with non-dental second-arch epithelium. Among the supplements, KSR is essential for the survival and adhesion of mDMCs, and both Egf and Fgf2 induced the expression of certain dental mesenchyme-related genes. Taken together, our results demonstrated that the transcriptomic changes responded to the alteration of odontogenic potential in cultured mDMCs and a new micromilieu partly retained this potential in vitro, providing insight into the long-term maintenance of odontogenic potential in mDMCs.
Quorum quenching quandary: resistance to antivirulence compounds (2011)

Quorum sensing (QS) is the regulation of gene expression in response to the concentration of small signal molecules, and its inactivation has been suggested to have great potential to attenuate microbial virulence. It is assumed that unlike antimicrobials, inhibition of QS should cause less Darwinian selection pressure for bacterial resistance. Using the opportunistic pathogen Pseudomonas aeruginosa, we demonstrate here that bacterial resistance arises rapidly to the best-characterized compound that inhibits QS (brominated furanone C-30) due to mutations that increase the efflux of C-30. Critically, the C-30-resistant mutant mexR was more pathogenic to Caenorhabditis elegans in the presence of C-30, and the same mutation arises in bacteria responsible for chronic cystic fibrosis infections. Therefore, bacteria may evolve resistance to many new pharmaceuticals thought impervious to resistance.
Thermodynamic Basis for Sequence-Specific Recognition of ssDNA by an Autoantibody (2001)

11F8 is a sequence-specific DNA binding monoclonal autoantibody previously isolated from an autoimmune lupus-prone mouse [Stevens, S. Y., and Glick, G. D. (1999) Biochemistry 38, 560-568]. This antibody, like many other lupus anti-DNAs, localizes to kidney tissue and eventually leads to renal damage through a process that first involves the binding of DNA antigens. A series of experiments were conducted to investigate the thermodynamic and structural basis by which this antibody discriminates between specific, noncognate, and nonspecific sequences. Sequence-specific binding occurs with a minimal dependence on the polyelectrolyte effect along with a favorable binding enthalpy reflecting the presence of base stacking and contacts to DNA bases. This favorable binding enthalpy apparently is derived from desolvation at the binding interface and is consistent with recent models of the nonclassical hydrophobic effect. Noncognate recognition is also driven by the nonclassical hydrophobic effect, but is accompanied by highly unfavorable entropies that are responsible for reduced affinity relative to the high-affinity consensus sequence. Nonspecific recognition is driven completely by the polyelectrolyte effect involving extensive electrostatic interactions with the phosphate backbone. Collectively, the data demonstrate the ability of 11F8 to adapt its mode of binding to the available DNA surface and provide a thermodynamic model for sequence-specific recognition of single-stranded DNA. The salient features of this model employ the paradigms invoked to explain protein.dsDNA, protein.RNA, and antibody.antigen binding.
Myocardial hypertrophy, cardiac β‐adrenoceptors and adenylate cyclase activity during sinoaortic denervation in dogs (1992)

1. The long-term effects of sinoaortic denervation on the development of left ventricular hypertrophy (assessed by the measurement of the ratio (R): heart weight/total body weight and LVT: left ventricular thickness), myocardial beta-adrenergic receptivity (measured by [125I]-cyanopindolol binding and adenylate cyclase activity) and plasma catecholamine levels (measured by h.p.l.c.) were investigated in three groups of dogs: normotensive controls (group 1), dogs made hypertensive by sinoaortic denervation and evaluated 1 (group 2) and 18 months (group 3) later. 2. Noradrenaline (NA) and adrenaline (A) plasma levels were 461 +/- 54 and 85 +/- 45 pg ml-1 in controls, 861 +/- 185 and 191 +/- 23 pg ml-1 in group 2 (P less than 0.05). They were normal in group 3 (426 +/- 132 and 110 +/- 16 pg ml-1). 3. R and LVT values were significantly (P less than 0.05) higher in sinoaortic denervated dogs (R = 7.7 +/- 0.1 and 7.8 +/- 0.2; LVT = 13.6 +/- 1.3 and 14.2 +/- 0.9 mm in groups 2 and 3 respectively) than in normotensive dogs (group 1: R = 6.7 +/- 0.1, LVT = 9.3 +/- 0.8 mm). 4. In group 1, the total number of beta-adrenoceptors (Bmax) was 37 +/- 11 and 29 +/- 6 fmol mg-1 protein in the left ventricle (LV) and right auricle (RA) respectively. In group 2, Bmax was significantly lower (10 +/- 3 in LV and 13 +/- 2 fmol mg-1 protein in RA, P less than 0.05) than in group 1. There was no difference between group 1 and group 3 (37 +/- 3 fmol mg-1 prot in LV and 31 +/- 3 fmol mg-1 protein in RA). 5. The percentage of beta 1-adrenoceptors was 82 +/- 4 in LV and 75 +/- 5 in RA in group 1. It was significantly lower (P less than 0.05) in groups 2 (LV: 33 +/- 6 and RA: 33 +/- 5) and 3 (LV: 59 +/- 3 and RA: 55 +/- 4). 6. Basal values of adenylate cyclase activity in LV significantly decreased after sinoaortic denervation.7. These data show that sinoaortic denervation is associated with left ventricular hypertrophy which appears early (1 month) and persists until 18 months despite the normalization of plasma catecholamine levels. The total number of myocardial beta-adrenoceptors is closely related to catecholamine levels but a selective decrease in beta 1-adrenoceptors is observed during cardiac hypertrophy. The fall in basal adenylate cyclase activity suggests that cardiac hypertrophy is associated with an impairment of transmembrane signalling.
HLA-C downregulation by HIV-1 adapts to host HLA genotype (2018)

HIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses. 128 replication competent viral isolates from 19 individuals with effective anti-retroviral therapy, show that a substantial minority of individuals harbor latent reservoir virus which strongly downregulates HLA-C. Untreated infections display no change in HLA-C downregulation during the first 6 months of infection, but variation between viral quasispecies can be detected in chronic infection. Vpu molecules cloned from plasma of 195 treatment naïve individuals in chronic infection demonstrate that downregulation of HLA-C adapts to host HLA genotype. HLA-C alleles differ in the pressure they exert for downregulation, and individuals with higher levels of HLA-C expression favor greater viral downregulation of HLA-C. Studies of primary and mutant molecules identify 5 residues in the transmembrane region of Vpu, and 4 residues in the transmembrane domain of HLA-C, which determine interactions between Vpu and HLA. The observed adaptation of Vpu-mediated downregulation to host genotype indicates that HLA-C alleles differ in likelihood of mediating a CTL response that is subverted by viral downregulation, and that preservation of HLA-C expression is favored in the absence of these responses. Finding that latent reservoir viruses can downregulate HLA-C could have implications for HIV-1 cure therapy approaches in some individuals.
The Origins and Consequences of Localized and Global Somatic Hypermutation (2018)

Abstract Cancer is a disease of the genome, but the dramatic inter-patient variability in mutation number is poorly understood. Tumours of the same type can differ by orders of magnitude in their mutation rate. To understand potential drivers and consequences of the underlying heterogeneity in mutation rate across tumours, we evaluated both local and global measures of mutation density: both single-stranded and double-stranded DNA breaks in 2,460 tumours of 38 cancer types. We find that SCNAs in thousands of genes are associated with elevated rates of point-mutations, while similarly point-mutation patterns in dozens of genes are associated with specific patterns of DNA double-stranded breaks. These candidate drivers of mutation density are enriched for known cancer drivers, and preferentially occur early in tumour evolution, appearing clonally in all cells of a tumour. To supplement this understanding of global mutation density, we developed and validated a tool called SeqKat to identify localized “rainstorms” of point-mutations (kataegis). We show that rates of kataegis differ by four orders of magnitude across tumour types, with malignant lymphomas showing the highest. Tumours with TP53 mutations were 2.6-times more likely to harbour a kataegic event than those without, and 239 SCNAs were associated with elevated rates of kataegis, including loss of the tumour-suppressor CDKN2A . We identify novel subtypes of kataegic events not associated with aberrant APOBEC activity, and find that these are localized to specific cellular regions, enriched for MYC-target genes. Kataegic events were associated with patient survival in some, but not all tumour types, highlighting a combination of global and tumour-type specific effects. Taken together, we reveal a landscape of genes driving localized and tumour-specific hyper-mutation, and reveal novel mutational processes at play in specific tumour types.