gebhart/patrepeval huggingface dataset:
Analysis of separable Markov-modulated rate models for information-handling systems (1991)

In many communication and computer systems, information arrives to a multiplexer, switch or information processor at a rate which fluctuates randomly, often with a high degree of correlation in time. The information is buffered for service (the server typically being a communication channel or processing unit) and the service rate may also vary randomly. Accurate capture of the statistical properties of these fluctuations is facilitated by modeling the arrival and service rates as superpositions of a number of independent finite state reversible Markov processes. We call such models separable Markov-modulated rate processes (MMRP). In this work a general mathematical model for separable MMRPs is presented, focusing on Markov-modulated continuous flow models. An efficient procedure for analyzing their performance is derived. It is shown that the ‘state explosion' problem typical of systems composed of a large number of subsystems, can be circumvented because of the separability property, which permits a decomposition of the equations for the equilibrium probabilities of these systems. The decomposition technique (generalizing a method proposed by Kosten) leads to a solution of the equilibrium equations expressed as a sum of terms in Kronecker product form. A key consequence of decomposition is that the computational complexity of the problem is vastly reduced for large systems. Examples are presented to illustrate the power of the solution technique.
Identification of differentially expressed genes in oral squamous cell carcinoma (2004)

Rapid advances in multimodality therapy have not significantly improved the overall 5-yr survival of oral cancer patients in the past two decades, thereby underscoring the need for molecular therapeutics. The development of new treatment strategies for more effective management of oral cancer requires identification of novel biological targets. Therefore, the aim of this study was to identify novel genes associated with oral tumorigenesis by comparing gene expression profile of oral squamous cell carcinomas (OSCCs) and matched nonmalignant oral epithelial tissues with differential display. Of the 180 differentially expressed cDNAs isolated, reamplified, and cloned into pGEMT-Easy Vector, 26 cDNAs were confirmed to be upregulated in OSCCs by reverse Northern blot analysis. The differentially expressed genes included components of immune system, signaling pathways, angiogenesis, cell structure, proliferation, apoptosis, cell-adhesion, and cellular metabolism. Reverse transcription (RT)-polymerase chain reaction (PCR) analysis of 15 OSCCs and matched nonmalignant oral tissues provided the first evidence that 14-3-3-zeta, melanoma metastasizing clone D (MEMD), KIAA0471, sperm protein 17 (SP17), TC21, and anti-TNF alpha antibody are upregulated in OSCCs. Immunohistochemical analysis confirmed overexpression of 14-3-3-zeta and TC21 protein, a member of the Ras family, in OSCCs as compared to histologically normal oral tissues validating the differential display analysis. Identification of six novel differentially expressed genes in oral tumors adds to the repertoire of genes associated with oral carcinogenesis and provides candidate potential biological targets for diagnosis and/or therapy. Further characterization of the 14 unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying oral tumorigenesis.
Catalytic synthesis of amines and N-containing heterocycles: Amidate complexes for selective C–N and C–C bond-forming reactions (2010)

The direct, 100 % atom-economic, and selective synthesis of amines is a challenging task that can be achieved, making use of early transition-metal catalysts. Here we report the synthesis and application of group 4 and 5 high-oxidation-state metal amidate complexes in catalytic C–N (hydroamination) and C–C (hydroaminoalkylation) bond-forming reactions to access substituted amines.
Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin (1995)

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.
Generation of Influenza A Viruses with Chimeric (Type A/B) Hemagglutinins (2003)

To gain insight into the intertypic incompatibility between type A and B influenza viruses, we focused on the hemagglutinin (HA) gene, systematically studying the compatibility of chimeric (type A/B) HAs with a type A genetic background. An attempt to generate a reassortant containing an intact type B HA segment in a type A virus background by reverse genetics was unsuccessful despite transcription of the type B HA segment by the type A polymerase complex. Although a type A virus with a chimeric HA segment comprising the entire coding sequence of the type B HA flanked by the noncoding sequence of the type A HA was viable, it replicated only marginally. Other chimeric viruses contained type A/B HAs possessing the type A noncoding region together with either the signal peptide or transmembrane/cytoplasmic region of type A virus or both, with the remaining regions derived from the type B HA. Each of these viruses grew to median tissue culture infectious doses of more than 10(5) per ml, but those with more type A HA regions replicated better, suggesting protein-protein interactions or increased HA segment incorporation into virions as contributing factors in the efficient growth of this series of viruses. All of these chimeric (A/B) HA viruses were attenuated in mice compared with wild-type A or B viruses. All animals intranasally immunized with a chimeric virus survived upon challenge with a lethal dose of wild-type type B virus. These results suggest a framework for the design of a novel live vaccine virus.
Protein kinase C activation leads to dephosphorylation of occludin and tight junction permeability increase in LLC-PK1 epithelial cell sheets (2000)

Activation of protein kinase C by exposure of LLC-PK1 renal epithelial cells to 10(-7) M TPA, a tumor promoting phorbol ester, results in a rapid and sustained increase in paracellular permeability as evidenced by a decrease in transepithelial electrical resistance. Occludin, the first identified transmembrane protein to be localized to the tight junction of both epithelial and endothelial cells is thought play an important role in tight junction barriers. Although transepithelial electrical resistance fell to less than 20% of initial values within 1 hour of TPA exposure, transmission electron microscopy showed no change in the gross morphology of the tight junction of cells treated with 10(-7) M TPA for up to 2 hours. Immunofluorescence microscopy revealed a more rapid change in the membrane distribution of ZO-1 compared to occludin in the TPA-treated cells. Immunoblot analysis indicated that occludin levels in total cell lysates as well as cytosolic, membrane (Triton-X soluble) and cytoskeletal (Triton-X insoluble) fractions remained unchanged for at least 2 hours in cells treated with 10(-7) M TPA compared to their corresponding control cells. As the phosphorylation state of occludin is thought to be important in both tight junction assembly and regulation, the effect of phorbol ester treatment on the phosphorylation of occludin was investigated. Surprisingly, activation of protein kinase C with 10(-7) M TPA resulted in a time-dependent decrease in threonine phosphorylation of occludin which correlated closely with the rapid decrease in transepithelial electrical resistance. This dephosphorylation of occludin, occurring after activation of a serine/threonine kinase by TPA, suggested that protein kinase C was not acting directly on this tight junction target protein. If occludin dephosphorylation is involved in increasing tight junction permeability, then protein kinase C is apparently further upstream in the signaling pathway regulating epithelial barrier function, with a downstream serine/threonine phosphatase acting upon occludin.
Integral three-dimensional video system (2001)

A three-dimensional video system based on integral photography using a micro-lens array is described. Four problems with the system and technical means to solve them are proposed. Especially, resolution characteristics including those of pickup and display are described in detail. The experimental system using television camera and liquid crystal display (LCD) provides full color and autostereoscopic 3-D images with full parallax in real time.
Luminescence of Copper-Activated Calcium and Strontium Orthophosphates (1959)

Copper produces a strong luminescence in . Luminescence in occurs only in the presence of small amounts of foreign ions such as Ca, Zn, Cd, Mg, or Al. These additions give rise to a new crystal phase which is probably isomorphous with . The emission peaks under excitation with 2537Aå of , , and of modified with Al are found at 4800, 5700, and 4950Aå, respectively. Sensitization occurs with Mn, giving rise to a red emission peak. The temperature dependence of the fluorescence is good, especially that of and partly substituted with Mg and Ca. Phosphor application in lamps presents difficulties due to the materials' sensitivity to air at binder bake‐out temperatures.
Noisy audio feature enhancement using audio-visual speech data (2002)

We investigate improving automatic speech recognition (ASR) in noisy conditions by enhancing noisy audio features using visual speech captured from the speaker's face. The enhancement is achieved by applying a linear filter to the concatenated vector of noisy audio and visual features, obtained by mean square error estimation of the clean audio features in a training stage. The performance of the enhanced audio features is evaluated on two ASR tasks: A connected digits task and speaker-independent, large-vocabulary, continuous speech recognition. In both cases and at sufficiently low signal-to-noise ratios (SNRs), ASR trained on the enhanced audio features significantly outperforms ASR trained on the noisy audio, achieving for example a 46% relative reduction in word error rate on the digits task at −3.5 dB SNR. However, the method fails to capture the full visual modality benefit to ASR, as demonstrated by its comparison to discriminant audio-visual feature fusion introduced in previous work.
Experimental realization of catalytic CH4 hydroxylation predicted for an iridium NNC pincer complex, demonstrating thermal, protic, and oxidant stability (2009)

A discrete, air, protic, and thermally stable (NNC)Ir(III) pincer complex was synthesized that catalytically activates the CH bond of methane in trifluoroacetic acid; functionalization using NaIO4 and KIO3 gives the oxy-ester.
Vitamin D3 binding protein required for in vitro activation of macrophages after alkylglycerol treatment of mouse peritoneal cells. (1991)

In vitro treatment of peritoneal cells with dodecylglycerol (DDG) in 10% foetal calf serum (FCS) supplemented medium RPMI-1640 results in a greatly enhanced Fc receptor-mediated phagocytic activity of macrophages. This macrophage activation process requires a serum factor in the alpha 2-globulin fraction. When mouse peritoneal cells were treated with 50 ng DDG/ml in a serum-free 0.1% egg albumin-supplemented medium RPMI-1640 (EA medium) for 30 min and cultured in EA medium containing electrophoretically fractionated alpha 2-globulin for 3 hr, a markedly enhanced activation of macrophages was observed. To improve fractionation of alpha 2-globulin, FCS was first precipitated with 50% saturated ammonium sulphate and then the supernatant electrophoretically fractionated. The resultant alpha 2-globulin fraction was unable to support activation of macrophages. Vitamin D3 binding protein (DBP) of the alpha 2-globulin fraction is known to be precipitable by 50% saturated ammonium sulphate. When human alpha 2-globulin was treated with antiserum against human DBP and used in a medium for cultivation of DDG-treated peritoneal cells, no significant activation of macrophages was observed. Cultivation of DDG-treated peritoneal cells in a medium containing a low concentration of purified human DBP (group specific component, Gc) produced a greatly enhanced ingestion activity of macrophages. Purified human Gc protein, when used in an EA medium for step-wise cultivation of DDG-treated B and untreated T cells, was efficiently converted to a macrophage-activating factor.
Antibacterial Effect of Cyanoacrylate Glue (1983)

Enbucrilate (butyl-2-cyanoacrylate; Histoacryl [West Germany], no comparable US product) is a tissue adhesive used in the management of corneal perforations that may have a therapeutic value in suppressing selective pathogens isolated, from corneal infections. In three patients with confirmed corneal infections, varying degrees of inhibition were observed. Bacteriostatic activity was most pronounced against gram-positive microorganisms, and no activity was observed against gram-negative organisms. It appears that this chemical adhesive provided an ancillary means of promoting healing of corneal perforations.
Capacitive Boosting for FPGA Interconnection Networks (2011)

FPGA interconnection network is implemented using nMOS pass transistor multiplexers. Since the threshold voltage drop across an nMOS device degrades the high logic value, the pMOS transistors of the downstream buffers do not turn fully off, making this approach suffer from static power consumption due to the short-circuit currents and reduced noise margins. The standard pMOS transistor pull-up in the active feedback of an inverter reduces the static power consumption but degrades the switching time and/or dynamic power consumption. We propose to use capacitive boosting to increase the gate voltage of the pass transistors, thus driving the multiplexer output to the full high voltage level at a faster rate than the pMOS pull-up can alone. This way, the signal transitions are accelerated and the short-circuit current of downstream buffers are cut off. The simulations carried out with Cadence indicate a reduction of at least 10% in propagation delay for the proposed circuit versus the standard one across 180nm, 130nm, 90nm, and 65nm technologies.
Potent and Tumor specific: Arming Bacteria With Therapeutic Proteins (2015)

Bacteria are perfect vessels for targeted cancer therapy. Conventional chemotherapy is limited by passive diffusion, and systemic administration causes severe side effects. Bacteria can overcome these obstacles by delivering therapeutic proteins specifically to tumors. Bacteria have been modified to produce proteins that directly kill cells, induce apoptosis via signaling pathways, and stimulate the immune system. These three modes of bacterial treatment have all been shown to reduce tumor growth in animal models. Bacteria have also been designed to convert nontoxic prodrugs to active therapeutic compounds. The ease of genetic manipulation enables creation of arrays of bacteria that release many new protein drugs. This versatility will allow targeting of multiple cancer pathways and will establish a platform for individualized cancer medicine.
Decorating single layer graphene oxide with electron donor and acceptor molecules for the study of photoinduced electron transfer (2013)

Graphene oxide decorated with an electron donor, zinc(II) phthalocyanine, and an electron acceptor, fullerene, has been synthesized, and photoinduced electron transfer leading to charge-separation is reported.
An Introduction to the Basic Principles of Magnetic Nerve Stimulation (1991)

Magnetic nerve stimulation is a new method for the noninvasive stimulation of neuromuscular tissue. The technique, developed at the University of Sheffield, United Kingdom, is being increasingly used for both clinical studies and basic research, with some 500 stimulators presently in use worldwide. This paper looks at the development of magnetic stimulation as a clinical tool. The basic physics principles of the technique are outlined, and the different magnetic field waveforms, coil geometrics, and orientations that can be used are discussed. The depth of penetration of magnetic stimulation is compared to that of conventional electrical stimulation using surface electrodes. It is shown that the former generates lower electric fields at the surface of the body, resulting in greater penetration and the ability to stimulate deep nerves without pain. Magnetic stimulation has several other advantages over electrical stimulation, including being able to stimulate the human brain without discomfort due to the magnetic fields passing through the skull without attenuation. These advantages, along with the limitations of the technique, are discussed. Finally, data relating to the safety of brain stimulation are summarised in terms of the electromagnetic parameters used. It is concluded that the present generation of magnetic stimulators do not cause acute hazards, provided their electrical and mechanical design meets the relevant electromedical safety standards.
Structural changes in histone H2A by methylglyoxal generate highly immunogenic amorphous aggregates with implications in auto-immune response in cancer (2015)

The role of aberrant protein modifications in cancer and its diagnosis have emerged as a promising research field. Nonenzymatic glyco-oxidation of proteins under oxidative stress has been associated with carcinogenesis through advanced glycation end products (AGE)-receptors for advanced glycation end products (RAGE) axis. Modified proteins that are immunogenic and stimulate cellular and humoral immune responses are being studied to develop early detection markers of cancer. This study has probed the structural alternations; leading to the formation of adducts and aggregates, in histone H2A upon in vitro modification by methylglyoxal (MG). The immunogenicity of modified histone H2A and its binding with cancer autoantibodies was also assessed. MG induced lysine side chain modifications, blocking of free amino groups and the formation of condensed cross structures in histone H2A; and its effect was inhibited by carbonyl scavengers. It led to the adduct formation and generation of N-epsilon-(carboxyethyl)lysine (CEL) and its decomposition forms as revealed by Matrix-assisted laser desorption ionization-mass spectrometry, high-performance liquid chromatography and LC-MS. MG-H2A showed amorphous aggregate formation under electron microscopy and altered binding with DNA in circular dichroism studies. The modified histone elicited high titer immunogen-specific antibodies in rabbits when compared with the native, thus pointing toward the generation of neo-epitopes in MG-H2A. The autoantibodies derived from cancer patients exhibited enhanced binding with MG-H2A as compared with the native histone in enzyme-linked immunosorbent assay and gel retardation assay. This reflects sharing of epitopes on MG-H2A and histones in cancer patients. The neo-epitopes on H2A may be responsible for induction and elevated levels of antibodies in cancer patients. Thus, MG-H2A may be considered as potential antigenic candidate for auto-immune response in cancer.
In Vivo Electroporation Enhances the Immunogenicity of Hepatitis C Virus Nonstructural 3/4A DNA by Increased Local DNA Uptake, Protein Expression, Inflammation, and Infiltration of CD3+ T Cells (2007)

The mechanisms by which in vivo electroporation (EP) improves the potency of i.m. DNA vaccination were characterized by using the hepatitis C virus nonstructural (NS) 3/4A gene. Following a standard i.m. injection of DNA with or without in vivo EP, plasmid levels peaked immediately at the site of injection and decreased by 4 logs the first week. In vivo EP did not promote plasmid persistence and, depending on the dose, the plasmid was cleared or almost cleared after 60 days. In vivo imaging and immunohistochemistry revealed that protein expression was restricted to the injection site despite the detection of significant levels of plasmid in adjacent muscle groups. In vivo EP increased and prolonged NS3/4A protein expression levels as well as an increased infiltration of CD3+ T cells at the injection site. These factors most likely additively contributed to the enhanced and broadened priming of NS3/4A-specific Abs, CD4+ T cells, CD8+ T cells, and gamma-IFN production. The primed CD8+ responses were functional in vivo, resulting in elimination of hepatitis C virus NS3/4A-expressing liver cells in transiently transgenic mice. Collectively, the enhanced protein expression and inflammation at the injection site following in vivo EP contributed to the priming of in vivo functional immune responses. These localized effects most likely help to insure that the strength and duration of the responses are maintained when the vaccine is tested in larger animals, including rabbits and humans. Thus, the combined effects mediated by in vivo EP serves as a potent adjuvant for the NS3/4A-based DNA vaccine.
Transcription Arrest at an Abasic Site in the Transcribed Strand of Template DNA (2006)

A dedicated excision repair pathway, termed transcription-coupled repair (TCR), targets the removal of DNA lesions from transcribed strands of expressed genes. Transcription arrest at the site of the lesion has been proposed as the first step for initiation of TCR. In support of this model, a strong correlation between arrest of transcription by a lesion in vitro and TCR of that lesion in vivo has been found in most cases analyzed. TCR has been reported for oxidative DNA damage; however, very little is known about how frequently occurring and spontaneous DNA damage, such as depurination and base deamination, affects progression of the transcription complex. We have previously determined that the oxidative lesion, thymine glycol, is a significant block to transcription by T7 RNA polymerase (T7 RNAP) but has no detectable effect on transcription by RNA polymerase II (RNAP II) in a reconstituted system with all of the required factors. Another oxidative lesion, 8-oxoguanine, only slightly blocked T7 RNAP and caused RNAP II to briefly pause at the lesion before bypassing it. Because an abasic site is an intermediate in the repair of oxidative damage, it was of interest to learn whether it arrested transcription. Using in vitro transcription assays and substrates containing a specifically positioned lesion, we found that an abasic site in the transcribed strand is a 60% block to transcription by T7 RNAP but nearly a complete block to transcription by mammalian RNAP II. An abasic site in the nontranscribed strand did not block either polymerase. Our results clearly indicate that an abasic site is a much stronger block to transcription than either a thymine glycol or an 8-oxoguanine. Because the predominant model for TCR postulates that only lesions that block RNAP will be subject to TCR, our findings suggest that the abasic site may be sufficient to initiate TCR in vivo.