gebhart/patrepeval huggingface dataset:
A Limited Memory Algorithm for Bound Constrained Optimization (1995)

An algorithm for solving large nonlinear optimization problems with simple bounds is described. It is based on the gradient projection method and uses a limited memory BFGS matrix to approximate the Hessian of the objective function. It is shown how to take advantage of the form of the limited memory approximation to implement the algorithm efficiently. The results of numerical tests on a set of large problems are reported.
Turbo cloning: a fast, efficient method for cloning PCR products and other blunt-ended DNA fragments into plasmids (1993)

The method uses a novel plasmid vector, p9lox5, containing a site-specific recombination sequence lox from the lox/Cre recombinase system of bacteriophage P1. There are two distinct stages. Firstly, vector and fragment DNAs are ligated intermolecularly under conditions of macromolecular crowding (15% polyethylene glycol 6000) which accelerate blunt-end joining a thousandfold. Secondly, circular recombinant molecules are efficiently excised from the ligation products by Cre recombinase acting on pairs of lox sites within directly repeated vector molecules flanking insert DNA. Recombinants are introduced into cells conventionally by transformation or electroporation. In both a model system and the cloning of PCR products, yields approaching those obtainable in cohesive-end cloning were achieved. Applications of the technique to cDNA library generation and recovery of DNA from archive material are discussed.
Rat and Mouse Proopio-melanocortin Gene Sequences Target Tissue-Specific Expression to the Pituitary Gland but not to the Hypothalamus of Transgenic Mice (1993)

The proopiomelanocortin (POMC) gene is expressed predominantly in corticotrophs of the pituitary anterior lobe, melanotrophs of the intermediate lobe and neurons of the arcuate nucleus of the hypothalamus. The different ontogeny of POMC mRNA as well as the complicated hormonal regulation of POMC gene expression in the three different cell types suggests a concerted interaction between several cis-acting elements in the POMC gene and transcription factors located in each of the three cell types. To investigate cell-specific elements in the POMC gene we tested two different constructs in transgenic mice. The construct -4000rPOMCLacZ, carrying 4 kb of the rat POMC promoter fused to the Escherichia coli beta-galactosidase gene, showed appropriate expression in melanotrophs in 50% of the mice analyzed. beta-Galactosidase activity was less evident in corticotrophs under basal environmental conditions. In brain, 7 out of 15 independently derived transgenic founders had ectopic expression of the transgene in different areas; however, none of the animals analyzed expressed beta-galactosidase in neurons of the arcuate nucleus. The construct HAL*, a 'tagged' 10.2-kb mouse genomic fragment, was more efficiently targeted to the pituitary. Using in situ hybridization, we detected uniform expression of HAL* in melanotrophs in 100% of the 6 pedigrees analyzed and transgenic mRNA levels paralleled those of the endogenous POMC mRNA. In corticotrophs, basal expression was low but after adrenalectomy HAL* mRNA levels were comparable to those of POMC. None of the 6 pedigrees had appropriate expression of HAL* in the brain; however, 2 lines had ectopic expression in the dentate gyrus of the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
IntMDCT - A link between perceptual and lossless audio coding (2002)

The Modified Discrete Cosine Transform (MDCT) is widely used in modem perceptual audio coding schemes. In this paper we present an integer approximation of this lapped transform, called IntMDCT, which is derived from the MDCT using the lifting scheme. This reversible integer transform inherits most of the attractive properties of the MDCT, exhibiting a good spectral representation of the audio signal, critical sampling and overlapping of blocks. This makes the IntMDCT well suited for both lossless audio coding as well as for combined perceptual and lossless audio coding. A scalable system is presented providing a lossless enhancement of perceptual audio coding schemes, such as MPEG-2 AAC.
Asthma (2001)

Asthma is a complex syndrome with many clinical phenotypes in both adults and children. Its major characteristics include a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. For many patients, the disease has its roots in infancy, and both genetic factors (atopy)1,2 and environmental factors (viruses,3 allergens,4 and occupational exposures5) contribute to its inception and evolution. To comprehend the pathogenetic mechanisms underlying the many variants of asthma, it is essential to identify factors that initiate, intensify, and modulate the inflammatory response of the airway and to determine how these immunologic and biologic processes produce the characteristic . . .
A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation (2005)

Signaling by receptor activator of NF-kappaB (nuclear factor-kappaB) ligand (RANKL) is essential for differentiation of bone marrow monocyte-macrophage lineage (BMM) cells into osteoclasts. Here, we show RANKL stimulation of BMM cells transiently increased the intracellular level of reactive oxygen species (ROS) through a signaling cascade involving TNF (tumor necrosis factor) receptor-associated factor (TRAF) 6, Rac1, and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) 1. A deficiency in TRAF6 or expression of a dominant-interfering mutant of TRAF6 blocks RANKL-mediated ROS production. Application of N-acetylcysteine (NAC) or blocking the activity of Nox, a protein leading to the formation of ROS, with diphenylene iodonium (DPI) inhibits the responses of BMM cells to RANKL, including ROS production, activation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK), and osteoclast differentiation. Moreover, both RANKL-mediated ROS production and osteoclast differentiation were completely blocked in precursors depleted of Nox1 activity by RNA interference or by expressing a dominant-negative mutant of Rac1. Together, these results indicate that ROSs act as an intracellular signal mediator for osteoclast differentiation.
A parallel design and implementation for backpropagation neural network using MIMD architecture (2002)

The paper illustrates a parallel backpropagation algorithm that depends upon a transputer network. Since the backpropagation algorithm is regarded as being communication intensive, a mechanism is developed to decrease the communication time overhead between different related processor elements. The developed parallel backpropagation algorithm is applied to the problem of printed Arabic character recognition. The experimental results revealed that the speed up approaches the maximum value of 15.2 when a network of 16-transputers is utilized.
<title>Multidimensional partial response for parallel readout optical memories</title> (1994)

We extend a serial communication technique, Partial Response (PR) precoding, to two and three dimensions to increase the capacity and signal separation in parallel readout optical memory systems. We also develop expressions for optimal 2D equalizers that improve signal separation by reshaping reconstructed pixels. We simulate and experimentally verify the performance of various forms of PR precoding in a coherent imaging readout system using 2D arrays of binary phase storage pixels. However, the techniques presented here may be applied to other readout systems and other storage values. With an equalizer, PR precoding yields a factor of two improvements in worst case signal separation over a system without precoding.
OC-025 Alisporivir inhibition of cellular cyclophilins disrupts hepatitis B virus (HBV) replication and this effect is further enhanced in combination with direct antiviral targeting HBV-DNA polymerase in vitro (2012)

Introduction Cyclophilins are intracellular proteins with enzymatic activity—peptidyl-prolyl-isomerase that plays a major role in the life cycle of Hepatitis C virus. By targeting host cyclophilins Alisporivir (DEB025) exerts potent anti-HCV activity in vitro and in clinical studies. We have recently shown in vitro that cyclophilin inhibition with Alisporivir or NIM811 also interferes with HBV replication, with Alisporivir having a greater effect than NIM811. To elucidate the underlying mechanisms, in the present study we compared in vitro the effects on HBV replication of Alisporivir alone, Alisporivir in combination with a potent antiviral targeting HBV-DNA polymerase, and in cells after selective knockdown of individual cyclophilins. Methods Stably (HepG2215) and transiently (HUH-7) transfected cells, producing full HBV virions and HBsAg particles, were treated with different Alisporivir concentrations (0.25/1.0/5.0/20 ug/ml) alone, Telbivudine alone, or combinations of Alisporivir and Telbivudine. To determine the involvement of individual cyclophilins, HepG2215 cells were transfected with siRNA-specific for cyclophilin (Cyp) A, C or D and additionally treated with Alisporivir. Cytoplasmic extracts and supernatants were harvested at baseline; 24, 48 and 72 h post-treatment. The kinetics of antiviral activity was assessed by quantitation of intracellular and secreted HBV-DNA (real-time qPCR) and HBsAg levels (ELISA). Results Alisporivir treatment resulted in dose-dependent reduction of intracellular and secreted HBV-DNA from HepG2215 and HUH-7 cells at all time points, by 70% (p=0.004) and 63% (p&lt;0.001), respectively, compared with untreated controls. The combination of Alisporivir and Telbivudine had greater effects in reducing intracellular (p=0.001) and secreted (p=0.028) HBV-DNA, and &gt;3-fold reduction of HBsAg vs either Alisporivir or Telbivudine alone. CypA, C or D expression was markedly reduced after transfection with corresponding siRNA, which was associated with significant decrease of HBV-DNA and HBsAg levels (p&lt;0.001). Alisporivir treatment of cells silenced for CypA, C or D further reduced HBV-DNA and HBsAg levels, with greater antiviral effects in CypC or CypD silenced cells, compared with CypA silenced cells (p&lt;0.001). Conclusion These results suggest that Alisporivir interferes with multiple sites of HBV replication and has synergistic antiviral activity with direct antiviral targeting viral DNA polymerase, such as Telbivudine. Competing interests None declared.
Histone-like proteins from fish are lethal to the parasitic dinoflagellate Amyloodinium ocellatum (2001)

Antimicrobial proteins were purified from acid extracts of rainbow trout (Oncorhynchus mykiss) and sunshine bass (Morone saxatilis male x M. chrysops female) skin, gill and spleen by reverse-phase HPLC. Mass spectrometry and amino acid sequence data suggest that these proteins are closely related to histone H2B and histone H1 and thus they were designated histone-like proteins (HLPs). These proteins were lethal to Amyloodinium ocellatum, which is one of the most important parasitic agents affecting fish. Antibiotic concentrations as low as 12.5 microg/ml were inhibitory. Activity was directed against the trophont (feeding) stage of the parasite, while the disseminative (dinospore) stage was unaffected. Thus, HLPs act unlike typical drugs used to treat amyloodiniosis, which usually target the dinospore. Both the ability of the parasite to infect host cells, as well as the ability to grow and differentiate after infection were severely inhibited. This is in contrast to magainin 2, which was similarly toxic to both the dinospore and trophont stages. These findings provide further evidence that histone-like proteins may be important defensive molecules in fish.
Glycation, Glycoxidation, and Cross-Linking of Collagen by Glucose: Kinetics, Mechanisms, and Inhibition of Late Stages of the Maillard Reaction (1994)

The Maillard or browning reaction between sugar and protein contributes to the increased chemical modification and cross-linking of long-lived tissue proteins in diabetes. To evaluate the role of glycation and oxidation in these reactions, we have studied the effects of oxidative and antioxidative conditions and various types of inhibitors on the reaction of glucose with rat tail tendon collagen in phosphate buffer at physiological pH and temperature. The chemical modifications of collagen that were measured included fructoselysine, the glycoxidation products N epsilon-(carboxymethyl)lysine and pentosidine and fluorescence. Collagen cross-linking was evaluated by analysis of cyanogen bromide peptides using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by changes in collagen solubilization on treatment with pepsin or sodium dodecylsulfate. Although glycation was unaffected, formation of glycoxidation products and cross-linking of collagen were inhibited by antioxidative conditions. The kinetics of formation of glycoxidation products proceeded with a short lag phase and were independent of the amount of Amadori adduct on the protein, suggesting that autoxidative degradation of glucose was a major contributor to glycoxidation and cross-linking reactions. Chelators, sulfhydryl compounds, antioxidants, and aminoguanidine also inhibited formation of glycoxidation products, generation of fluorescence, and cross-linking of collagen without significant effect on the extent of glycation of the protein. We conclude that autoxidation of glucose or Amadori compounds on protein plays a major role in the formation of glycoxidation products and cross-liking of collagen by glucose in vitro and that chelators, sulfhydryl compounds, antioxidants, and aminoguanidine act as uncouplers of glycation from subsequent glycoxidation and cross-linking reactions.
Perturbation of the temperature distribution in microwave irradiated tissue due to the presence of metallic thermometers (1987)

To date, satisfactory thermal dosimetry during the clinical application of localized hyperthermia can only be achieved using invasive thermometry. However the presence of commonly used metallic thermometers, such as thermocouples, may lead to the distortion of the temperature field due to self-heating of the probe under microwave irradiation. A computer simulation of the effect of this self-heating on the steady-state temperature distribution in plane-microwave irradiated homogeneous tissue has been undertaken and the significance of the effect for clinical hyperthermia dosimetry is assessed. The results indicate that a distortion of the temperature field in the neighborhood of the thermometer by several degrees can occur under adverse conditions.
Overexpression of the vaccinia virus A38L integral membrane protein promotes Ca2+ influx into infected cells (1996)

The vaccinia virus Western Reserve A38L protein is a hydrophobic integral membrane glycoprotein with amino acid similarity to mammalian integrin-associated protein. The protein has an N-terminal immunoglobulin superfamily domain, followed by five membrane-spanning domains and a short cytoplasmic tail. Deletion of the protein reduces virus plaque size but does not affect virus virulence (J. E. Parkinson, C. M. Sanderson, and G. L. Smith, Virology, in press). In this study, we have used a recombinant vaccinia virus in which the A38L gene may be inducibly overexpressed by addition of isopropyl-beta-D-thiogalactopyranoside (IPTG), to demonstrate that overexpression of the vaccinia virus A38L gene produces drastic changes in the morphology, permeability, and adhesion of infected cells. In particular, A38L overexpression caused swelling of cells, marginalization of nuclear chromatin, and vacuolization of the endoplasmic reticulum, features characteristic of cell necrosis. By 18 h postinfection, cells become permeable and lytic as defined by the free entry of propidium iodide and loss of the cytoplasmic enzyme lactate dehydrogenase. Chelation of extracellular Ca2+ 22 h postinfection inhibited further release of lactate dehydrogenase, showing that Ca2+ influx was required for A38L-induced lysis. Direct measurement of 45Ca2+ influx showed that the rate of Ca2+ uptake was directly related to the period of A38L induction. The A38L protein, therefore, promotes the formation of pores within the plasma membrane of cells, and these pores facilitate Ca2+ entry and induce necrosis. Addition of rifampin inhibited virus assembly but not the ability of A38L to induce necrosis, indicating that pore formation is independent of viral morphogenesis. Finally, overexpression of the A38L protein resulted in a reduced plaque size and a threefold decrease in production of infective particles in vitro. The A38L protein represents the first example of a virus protein which directly or indirectly promotes the influx of extracellular Ca2+.
The impact of directional antennas on energy-aware, session-based multicasting in ad hoc wireless networks (2002)

In our earlier studies we developed several algorithms for broadcast and multicast tree construction for session traffic in all-wireless networks. The Broadcast Incremental Power (BIP) and Multicast Incremental Power (MIP) algorithms are "node-based" schemes that exploit the "wireless multicast advantage" provided by the use of omnidirectional antennas. In this paper, we study broadcasting and multicasting when directional antennas are used. Alternative approaches to implementing algorithms based on BIP and MIP are presented, and their energy efficiency is evaluated. It is shown that considerable savings in energy can be achieved by using directional antennas, especially by using the Directional-BIP (D-BIP) and Directional MIP (D-MIP) schemes, which exploit directional antenna properties throughout the tree construction process.
Fluorescence Reporters for Phosphodiesterase Activity (1997)

A sensitive indicator of nuclease activity is the fluorescence behavior of phosphodiesters 1 and 2. Although 1 and 2 do not fluoresce due to intramolecular quenching, the strongly fluorescent naphthyl phosphates and naphthols are liberated upon hydrolysis. This gives rise to an extremely strong increase in fluorescence intensity. Combined application of 1 and 2 allows detection of phosphatase in addition to phosphodiesterase activity. f = fluorophore, q = quencher.
Markers of Hemostatic System Activation during Thromboprophylaxis with Recombinant Hirudin in Total Hip Replacement (1996)

Coagulation activation markers were studied in 148 patients undergoing total hip replacement under recombinant-hirudin (Desirudin, Revasc) prophylaxis with the aim of investigating the efficacy and safety of this anticoagulant compared with heparin in terms of biological effects on coagulation variables and bleeding. Hirudin (10, 15 or 20 mg s.c. b.i.d.) or unfractionated heparin (5000 IU s.c. t.i.d.) was administered immediately before surgery and continued for 8-12 days. Activated partial thromboplastin time (aPTT), prothrombin activation fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer were measured at baseline and on postoperative days 1,3 and 6, immediately before the morning injection. In comparison with baseline values, heparin had little effect on aPTT whereas the three hirudin doses prolonged aPTT significantly with no differences among the three doses. Moreover, there were no group differences in perioperative or cumulative blood loss or transfusion requirements. F1 + 2 fragment, TAT and D-dimer plasma levels were higher than at baseline during the entire postoperative period, with different trends (F1 + 2 increasing, TAT decreasing, D-dimer increasing, decreasing and then increasing again), but without significant differences among the four treatment groups. Our findings suggest that specific inhibition of thrombin seems a safe and efficacious mode of blocking thrombin activity after hip surgery although it does not prevent thrombin generation.
Progressive video streaming over 2G and 3G wireless systems (2002)

A progressive video codec can be designed to be finely scalable, that is, it can produce one fully embedded bitstream which can be decoded at any intermediate rate up to the full target rate, producing progressively better video quality with increased bit-rate. Video scalability is an attractive feature that not only provides bit-rate adaptability to different bandwidth conditions over a heterogeneous network but also provides a framework for introducing graceful degradation in video quality in the presence of bit errors. The priority of the bits in a progressive video bitstream is, by design, well defined. Thus, efficient channel coding schemes can be designed. In this paper, we propose an unequal error protection scheme in the application layer for the video bitstream that works in concatenation with the channel codes in the physical layer of state-of-the-art cellular systems and demonstrate that progressive video streaming can be achieved over standard compliant second generation (2G) (and beyond) cellular systems without having to modify the physical layer of the systems. The channel protection scheme described would also work for a layered coder or for a coder where one could prioritize the data from the most to the least important.
Virus‐induced autoimmune disease: transgenic approach to mimic insulin‐dependent diabetes mellitus and other autoimmune diseases: (1996)

The technology of cloning viral genes and expressing them in vivo under cell-specific promoters allows to dissect the role of viruses, host self proteins, host genetics and immune responses in the complex etiology of autoimmune disease. Expression of a viral transgene, that is really a marker for a host "self" protein per se in beta cells of the islets of Langerhans, need not cause disease. In our model, expression of a viral gene was not associated with disease over the lifetime of the animal. However, when the host becomes infected with a virus encoding the same gene as the transgene or one closely related to it, a resultant immune response directed against the virus also recognizes the transgene leading to progressive T-cell-mediated response and destruction of the tissue expressing the viral ("self") gene, leading to autoimmune disease. This multifactorial process is influenced by whether the viral transgene is expressed in the thymus as well as in the disease-related cell or target tissue. Thymic expression influences negative selection of responder lymphocytes and thus delays the onset of the autoimmune disorder. Further, the MHC haplotype or other background genes of an individual undergoing autoimmune dysfunction play a role in the affinity of binding of the transgene products to the MHC molecule and influence the degree of negative selection that occurs, thereby influencing the vigor of the resulting immune response. The current ability to express host or viral genes in unique cell populations, and to make double- or triple-tg mice in which various cytokine genes or lymphocyte activation genes can be expressed along with the viral gene, offers a unique possibility for molecular dissection of autoimmunity. With the information on hand, approaches to the prevention and treatment of human autoimmune disease are likely to be uncovered. Finally, animal models are available in which the onset, progression and control of molecular mimicry can be evaluated. Future studies should define roles played by cytokines, bystander and immune-specific cross-reactivity to viruses and other microbes in several autoimmune diseases.