gebhart/patrepeval huggingface dataset:
Amplitude and frequency modulation of metabolic signals in leukocytes: synergistic role of IFN-gamma in IL-6- and IL-2-mediated cell activation. (1999)

Many stimuli cause intracellular concentration oscillations of second messengers or metabolites, which, in turn, may encode information in their amplitudes and frequencies. We now test the hypothesis that synergistic cellular responses to dual cytokine exposure correlate with cross-talk between metabolic signaling pathways of leukocytes. Polarized RAW264.7 macrophages and human neutrophils and monocytes exhibited NAD(P)H autofluorescence oscillation periods of congruent with20 s. IFN-gamma tripled the NAD(P)H oscillatory amplitude for these cells. Although IL-6 had no effect, incubation of cells with IFN-gamma and IL-6 increased both oscillatory amplitude and frequency. Parallel changes were noted after treatment with IFN-gamma and IL-2. However, IL-1beta and TNF-alpha did not display frequency doubling with or without IFN-gamma exposure. To determine whether frequency doubling required complete IFN-gamma signaling or simply metabolic amplitude modulation, an electric field was applied to cells at NAD(P)H troughs, which has been shown to enhance NAD(P)H amplitudes. Electric field application led to frequency doubling in the presence of IL-6 or IL-2 alone, suggesting that amplitude modulation is crucial to synergism. Because NADPH participates in electron trafficking to NO, we tested NO production during cytokine exposure. Although IL-6 and IL-2 alone had no effect, IFN-gamma plus IL-6 and IFN-gamma plus IL-2 enhanced NO release in comparison to IFN-gamma treatment alone. When NO production was examined for single cells, it incrementally increased with the same phase and period as NAD(P)H. We suggest that amplitude and frequency modulation of cellular metabolic oscillations contribute to intracellular signaling synergy and entrain NO production.
Peptide libraries: Determination of relative reaction rates of protected amino acids in competitive couplings (1994)

In the solid phase preparation of synthetic peptide libraries, equimolarity of the resultant peptides in the mixture simplifies the identification of active compounds. Two primary methods for the preparation of combinatorial peptide mixtures are currently used. In the first method, the starting resin is divided into equal aliquots, individual amino acids are coupled to each aliquot, and the resin is then recombined. This process is repeated for each position. However, due to the physical process, each resin bead contains only one peptide sequence. Statistically, for mixtures of longer sequences, an ever-increasing amount of resin is necessary to ensure complete representation of each peptide in the library. Thus, each peptide will be represented in the library if a sufficient number of resin beads are used. In addition, the concentration of each peptide in the library depends on both the number of mixture positions in the library and the amount of resin used. In the second method, mixtures of amino acids are coupled simultaneously at each addition step. The proportion of each amino acid in the reaction mixture is varied inversely to its reaction rate such that, ideally, an equimolar mixture of each peptide is synthesized. An advantage of this method over the previous method is that each peptide is ensured to be represented in the library, although not necessarily in equimolar amounts. It is known that not only do the coupling rates of each amino acid vary, but the coupling rates of individual amino acids also change when coupled to different amino acid resins.(ABSTRACT TRUNCATED AT 250 WORDS)
Electron microscopic visualization of the RecA protein-mediated pairing and branch migration phases of DNA strand exchange. (1987)

The RecA protein of Escherichia coli will drive the pairing and exchange of strands between homologous DNA molecules in a reaction stimulated by single-stranded binding protein. Here, reactions utilizing three homologous DNA pairs which can undergo both paranemic and plectonemic joining were examined by electron microscopy: supertwisted double-stranded (ds) DNA and linear single-stranded (ss) DNA, linear dsDNA and circular ssDNA, and linear dsDNA and colinear ssDNA. Several major observations were: (i) with RecA protein bound to the DNA, plectonemic joints were ultrastructurally indistinguishable from paranemic joints; (ii) complexes which appeared to be joined both paranemically and plectonemically were present in these reactions in roughly equal numbers; and (iii) in complexes undergoing strand exchange, both DNA partners were often enveloped within a RecA protein filament consisting of hundreds of RecA protein monomers and several kilobases of DNA. These observations suggest that, following RecA protein-ssDNA filament formation, strand exchange proceeds by a pathway that can be divided structurally into three phases: pairing, envelopment/exchange, and release of the products.
Exposure‐Response Analysis in Patients With Schizophrenia to Assess the Effect of Asenapine on QTc Prolongation (2009)

An exposure-response (E-R) analysis using linear mixed effects modeling was conducted on data from a thorough QTc trial for asenapine in 148 patients with schizophrenia. In a parallel design, patients received asenapine 5 mg twice daily (BID) for 10 days (10d) followed by 10 mg BID (6d), asenapine 15 mg BID (10d) followed by 20 mg BID (6d), quetiapine 375 mg BID (for assay sensitivity; 16d) or placebo (16d). Triplicate 12-lead electrocardiograms and concentration measurements were obtained on day -1 (baseline), 1, 10, and 16 at 8 scheduled times on each day. At mean C(max) for all asenapine doses, the E-R model predicted that the mean QTcF increase was less than 5 milliseconds, the International Conference on Harmonisation-established threshold for clinical concern. The model predicted a mean increase of 7 to 8 milliseconds for quetiapine. The corresponding upper bounds of the 95% confidence intervals were 7.5 milliseconds and 11.2 milliseconds for asenapine and quetiapine, respectively.
Synthesis of a Zinc(II) Imidazolium Dicarboxylate Ligand Metal−Organic Framework (MOF): a Potential Precursor to MOF-Tethered N-Heterocyclic Carbene Compounds (2010)

Two new isomeric dinitrile ligands containing imidazolium salt cores have been synthesized from cyanoanilines in good yield. These have been converted to the corresponding dicarboxylic acids using hydrobromic acid, or the dicarboxylic acids were synthesized directly from the analogous cyanoaniline starting material in a two-step, one-pot reaction. The crystal structures of three of the four compounds are reported. Two reaction pathways with metals are possible for the dicarboxylic acids, initially giving rise to metal carboxylate based metal-organic frameworks (MOFs) as described in this work or N-heterocyclic carbene (NHC) metal complexes en route to the synthesis of MOFs containing tethered NHC complexes. The reaction of 1,3-bis(4-carboxyphenyl)imidazolium bromide with zinc nitrate in dimethylformamide (DMF) gave a one-dimensional (1D) MOF containing the intact imidazolium salt. The potentially porous structure, formed from close packing of the 1D necklace-type polymers, contains channels occupied by disordered DMF solvate molecules. A formate anion also bridges the zinc secondary building units in the 1D polymer, which has an undulating structure resulting from the U-shaped conformation of the dicarboxylate imidazolium ligand.
Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. (1997)

To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP-generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE- neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and "aggrecanase."
Towards non-stationary model-based noise adaptation for large vocabulary speech recognition (2002)

Recognition rates of speech recognition systems are known to degrade substantially when there is a mismatch between training and deployment environments. One approach to tackling this problem is to transform the acoustic models based on the channel distortion and noise characteristics of the new environment. Currently, most model adaptation strategies assume that the noise characteristics are stationary. We present results for using multiple noise distributions for the Whisper large vocabulary speech recognition system. The vector Taylor series method for adaptation of the distributions is used, and either a weighted average of the noise states or the locally best noise states is used. Our results indicate that for certain types of noise, significant gains in recognition accuracy can be achieved.
Molecular cloning, characterization, and elicitation of acetyl-CoA carboxylase from alfalfa. (1994)

Acetyl-CoA carboxylase [ACCase; acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] catalyzes the ATP-dependent carboxylation of acetyl CoA to produce malonyl CoA. In plants, malonyl CoA is needed for plastid localized fatty acid biosynthesis and for a variety of pathways in the cytoplasm including flavonoid biosynthesis. We have determined the full nucleotide sequence of an ACCase from alfalfa, which appears to represent a cytoplasmic isozyme. Partial cDNAs were isolated from a cDNA library of suspension culture cells that had been elicited for isoflavonoid phytoalexin synthesis. The full-length sequence was obtained by primer extension and amplification of the cDNA with synthetic primers. The sequence codes for a protein of 2257 amino acids with a calculated M(r) of 252,039. The biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase domains, respectively, show approximately 72%, 50%, and 65% sequence similarity to those of animal, diatom, and yeast ACCase sequences. ACCase enzyme activity and transcripts are induced severalfold upon addition of yeast or fungal elicitors to alfalfa cell cultures.
Development of a Camera-Based Forward Collision Alert System (2011)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Forward Collision Alert (or Forward Collision Warning) systems provide alerts intended to assist drivers in avoiding or mitigating the harm caused by rear-end crashes. These systems currently use front-grille mounted, forward-looking radar devices as the primary sensor. In contrast, Lane Departure Warning (LDW) systems employ forward-looking cameras mounted behind the windshield to monitor lane markings ahead and warn drivers of unintended lane violations. The increasing imaging sensor resolution and processing capability of forward-looking cameras, as well recent important advances in machine vision algorithms, have pushed the state-of-the-art for camera-based features. Consequently, camera-based systems are emerging as a key crash avoidance system component in both a primary and supporting sensing role. There are currently no production vehicles with cameras used as the sole FCA sensing device. This paper discusses the development of a camera-based FCA system that uses a camera in place of a radar device for sensing rear-end crash situations. This paper provides an overview of the system, including how the system detects vehicles, tracks vehicles, projects collision course trajectories, and estimates time-to-collision (TTC) using image scale change. Results from test track and public road testing support the deployment of a camera-based FCA system, and indicate this system would meet the United States Department of Transportation New Car Assessment Program (NCAP) Forward Collision Warning confirmation test requirements. Furthermore, the conditions under which most rear-end crashes occur suggests that this system provides a promising approach to reduce the harm caused by rear-end crashes.&lt;/div&gt;&lt;/div&gt;
The efficacy of nefazodone augmentation for treatment-resistant depression with anxiety symptoms or anxiety disorder (2003)

Depression that fails to respond to multiple antidepressant trials, particularly when accompanied by anxiety, constitutes a difficult treatment challenge. Those with anxious depression may be less likely to respond to treatment than their cohorts without anxiety. Anxiety symptoms also predict a higher rate of suicide, particularly if the symptoms do not improve early in the course of treatment. Eleven consenting outpatients with treatment-resistant depression and/or comorbid anxiety disorders were treated with nefazodone, slowly added to their ongoing treatment regimens. Doses were initiated at 50 mg a day and slowly increased by 50 mg increments until an optimum response was achieved. The Clinical Global Impression of Improvement (CGI) Scale was employed to monitor the medication effects. In all 11 cases, nefazodone was efficacious and well tolerated in the treatment of both depressive and anxiety components. After nefazodone augmentation, the mean CGI score for combined depression and anxiety symptoms was (+/-sd) 1.52 (0.52) on a scale from 1 (very much better) to 7 (very much worse). Seven of the 11 cases achieved complete remission of depressive symptoms (chi(2)=11.55, P<.005) and 9 of the 11 cases, complete remission of anxiety symptoms (chi(2)=15.23, P<.0005). The mean effective dose for nefazodone (mean+/-sd) was 200.0 (34.2) mg a day (range 50-300 mg a day). Nefazodone's unique pharmacologic profile may explain its unusual efficacy in these cases of treatment-resistant major depression.
Simplifying and isolating failure-inducing input (2002)

Given some test case, a program fails. Which circumstances of the test case are responsible for the particular failure? The delta debugging algorithm generalizes and simplifies the failing test case to a minimal test case that still produces the failure. It also isolates the difference between a passing and a failing test case. In a case study, the Mozilla Web browser crashed after 95 user actions. Our prototype implementation automatically simplified the input to three relevant user actions. Likewise, it simplified 896 lines of HTML to the single line that caused the failure. The case study required 139 automated test runs or 35 minutes on a 500 MHz PC.
A data-driven VLSI array for arbitrary algorithms (1988)

The design of specialized processing array architectures, capable of executing any given arbitrary algorithm, is proposed. An approach is adopted in which the algorithm is first represented in the form of a dataflow graph and then mapped onto the specialized processor array. The processors in this array execute the operations included in the corresponding nodes (or subsets of nodes) of the dataflow graph, while regular interconnections of these elements serve as edges of the graph. To speed up the execution, the proposed array allows the generation of computation fronts and their cancellation at a later time, depending on the arriving data operands; thus it is called a data-driven array. The structure of the basic cell and its programming are examined. Some design details are presented for two selected blocks, the instruction memory and the flag array. A scheme for mapping a dataflow graph (program) onto a hexagonally connected array is described and analyzed. Two distinct performance measures-mapping efficiency and array utilization-and some performance results are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transfer of foreign genes into intact maize cells with high-velocity microprojectiles (1988)

This report describes a process for delivering foreign genes into maize cells that does not require the removal of cell walls and is capable of delivering DNA into embryogenic and nonembryogenic tissues. Plasmid harboring a chimeric chloramphenicol acetyltransferase (CAT) gene was adsorbed to the surface of microscopic tungsten particles (microprojectiles). These microprojectiles were then accelerated to velocities sufficient for penetrating the cell walls and membranes of maize cells in suspension culture. High levels of CAT activity were consistently observed after bombardment of cell cultures of the cultivar Black Mexican Sweet, which were comparable to CAT levels observed after electroporation of protoplasts. Measurable increases in CAT levels were also observed in two embryogenic cell lines after bombardment. Gene expression was observed only when an intron from the alcohol dehydrogenase 1 gene of maize was ligated between the 35S promoter and the CAT coding region. CAT activity was detected in cell cultures bombarded with microprojectiles with an average diameter of 1.2 mum, but not after bombardment with microprojectiles 0.6 or 2.4 mum in diameter. Bombarding the same sample several times was found to markedly enhance CAT activity. These results demonstrate that the particle bombardment process can be used to deliver foreign DNA into intact cells of maize. Because this process circumvents the difficulties associated with regenerating whole plants from protoplasts, the particle bombardment process may provide significant advantages over existing DNA delivery methods for the production of transgenic maize plants. In addition, the process should be of value for studying transient and stable gene expression within intact cells and tissues.
Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review (1999)

The aims of this systematic literature review are to estimate termination rates after prenatal diagnosis of one of five conditions: Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes, and to determine the extent to which rates vary across conditions and with year of publication. Papers were included if they reported (i) numbers of prenatally diagnosed conditions that were terminated, (ii) at least five cases diagnosed with one of the five specified conditions, and (iii) were published between 1980 and 1998. 20 papers were found which met the inclusion criteria. Termination rates varied across conditions. They were highest following a prenatal diagnosis of Down syndrome (92 per cent; CI: 91 per cent to 93 per cent) and lowest following diagnosis of Klinefelter syndrome (58 per cent; CI: 50 per cent to 66 per cent). Where comparisons could be made, termination rates were similar in the 1990s to those reported in the 1980s.
Escherichia coli K-12 mutants deficient in uracil-DNA glycosylase (1978)

A new assay specific for uracil-DNA glycosylase is described, Escherichia coli mutants partially and totally deficient in uracil-DNA glycosylase activity have been isolated by using this assay in mass-screening procedures. These have been designated ung mutants. The ung gene maps between tyrA and nadB on the E. coli chromosome. T4 phage containing uracil in their DNA grow on the most glycosylase-deficient hosts but are unable to grow on wild-type bacteria. This provides a simple spot test for the ung genotype. The ung mutants show slightly higher rates of spontaneous mutation to antibiotic resistance. Taken together, these results suggest a central role for uracil-DNA glycosylase in the initiation of an excision repair pathway for the exclusion of uracil from DNA.
Biomedical Applications of Layer‐by‐Layer Assembly: From Biomimetics to Tissue Engineering (2006)

Abstract The design of advanced, nanostructured materials at the molecular level is of tremendous interest for the scientific and engineering communities because of the broad application of these materials in the biomedical field. Among the available techniques, the layer‐by‐layer assembly method introduced by Decher and co‐workers in 1992 has attracted extensive attention because it possesses extraordinary advantages for biomedical applications: ease of preparation, versatility, capability of incorporating high loadings of different types of biomolecules in the films, fine control over the materials' structure, and robustness of the products under ambient and physiological conditions. In this context, a systematic review of current research on biomedical applications of layer‐by‐layer assembly is presented. The structure and bioactivity of biomolecules in thin films fabricated by layer‐by‐layer assembly are introduced. The applications of layer‐by‐layer assembly in biomimetics, biosensors, drug delivery, protein and cell adhesion, mediation of cellular functions, and implantable materials are addressed. Future developments in the field of biomedical applications of layer‐by‐layer assembly are also discussed.
Modeling deformable objects from a single depth camera (2009)

We propose a novel approach to reconstruct complete 3D deformable models over time by a single depth camera, provided that most parts of the models are observed by the camera at least once. The core of this algorithm is based on the assumption that the deformation is continuous and predictable in a short temporal interval. While the camera can only capture part of a whole surface at any time instant, partial surfaces reconstructed from different times are assembled together to form a complete 3D surface for each time instant, even when the shape is under severe deformation. A mesh warping algorithm based on linear mesh deformation is used to align different partial surfaces. A volumetric method is then used to combine partial surfaces, fix missing holes, and smooth alignment errors. Our experiment shows that this approach is able to reconstruct visually plausible 3D surface deformation results with a single camera.