gebhart/patrepeval huggingface dataset:
New flow cytometric assays for monitoring cell-mediated cytotoxicity (2010)

The exact immunologic responses after vaccination that result in effective antitumor immunity have not yet been fully elucidated and the data from ex vivo T-cell assays have not yet defined adequate surrogate markers for clinical efficacy. A more detailed knowledge of the specific immune responses that correlate with positive clinical outcomes should help to develop better or novel strategies to effectively activate the immune system against tumors. Furthermore, clinically relevant material is often limited and, thus, precludes the ability to perform multiple assays. The two main assays currently used to monitor lymphocyte-mediated cytoxicity in cancer patients are the (51)Cr-release assay and IFN-gamma ELISpot assay. The former has a number of disadvantages, including low sensitivity, poor labeling and high spontaneous release of isotope from some tumor target cells. Additional problems with the (51)Cr-release assay include difficulty in obtaining autologous tumor targets, and biohazard and disposal problems for the isotope. The ELISpot assays do not directly measure cytotoxic activity and are, therefore, a surrogate marker of cyotoxic capacity of effector T cells. Furthermore, they do not assess cytotoxicity mediated by the production of the TNF family of death ligands by the cytotoxic cells. Therefore, assays that allow for the simultaneous measurement of several parameters may be more advantageous for clinical monitoring. In this respect, multifactor flow cytometry-based assays are a valid addition to the currently available immunologic monitoring assays. Use of these assays will enable detection and enumeration of tumor-specific cytotoxic T lymphocytes and their specific effector functions and any correlations with clinical responses. Comprehensive, multifactor analysis of effector cell responses after vaccination may help to detect factors that determine the success or failure of a vaccine and its immunological potency.
Variational Approach to Hard Sphere Segregation under Gravity (2002)

It is demonstrated that the minimization of the free energy functional for hard spheres and hard disks yields the result that excited granular materials under gravity segregate not only in the widely known "Brazil nut" fashion, i.e., with the larger particles rising to the top, but also in reverse "Brazil nut" fashion. Specifically, the local density approximation is used to investigate the crossover between the two types of segregation occurring in the liquid state, and the results are found to agree qualitatively with previously published results of simulation and of a simple model based on condensation.
Phosphorescent Pt(II) and Pd(II) Complexes for Efficient, High‐Color‐Quality, and Stable OLEDs (2016)

Phosphorescent organic light-emitting diodes (OLEDs) are leading candidates for next-generation displays and solid-state lighting technologies. Much of the academic and commercial pursuits in phosphorescent OLEDs have been dominated by Ir(III) complexes. Over the past decade recent developments have enabled square planar Pt(II) and Pd(II) complexes to meet or exceed the performance of Ir complexes in many aspects. In particular, the development of N-heterocyclic carbene-based emitters and tetradentate cyclometalated Pt and Pd complexes have significantly improved the emission efficiency and reduced their radiative lifetimes making them competitive with the best reported Ir complexes. Furthermore, their unique and diverse molecular design possibilities have enabled exciting photophysical attributes including narrower emission spectra, excimer -based white emission, and thermally activated delayed fluorescence. These developments have enabled the fabrication of efficient and "pure" blue OLEDs, single-doped white devices with EQEs of over 25% and high CRI, and device operational lifetimes which show early promise that square planar metal complexes can be stable enough for commercialization. These accomplishments have brought Pt complexes to the forefront of academic research. The molecular design strategies, photophysical characteristics, and device performance resulting from the major advancements in emissive Pt and Pd square planar complexes are discussed.
Re-evaluation of the roles of DROSHA , Exportin 5 , and DICER in microRNA biogenesis (2016)

Biogenesis of canonical microRNAs (miRNAs) involves multiple steps: nuclear processing of primary miRNA (pri-miRNA) by DROSHA, nuclear export of precursor miRNA (pre-miRNA) by Export in 5 (XPO5), and cytoplasmic processing of pre-miRNA by DICER. To gain a deeper understanding of the contribution of each of these maturation steps, we deleted DROSHA, XPO5, and DICER in the same human cell line, and analyzed their effects on miRNA biogenesis. Canonical miRNA production was completely abolished in DROSHA-deleted cells, whereas we detected a few DROSHA-independent miRNAs including three previously unidentified noncanonical miRNAs (miR-7706, miR-3615, and miR-1254). In contrast to DROSHA knockout, many canonical miRNAs were still detected without DICER albeit at markedly reduced levels. In the absence of DICER, pre-miRNAs are loaded directly onto AGO and trimmed at the 3' end, yielding miRNAs from the 5' strand (5p miRNAs). Interestingly, in XPO5 knockout cells, most miRNAs are affected only modestly, suggesting that XPO5 is necessary but not critical for miRNA maturation. Our study demonstrates an essential role of DROSHA and an important contribution of DICER in the canonical miRNA pathway, and reveals that the function of XPO5 can be complemented by alternative mechanisms. Thus, this study allows us to understand differential contributions of key biogenesis factors, and provides with valuable resources for miRNA research.
Low power wireless communication and signal processing circuits for distributed microsensors (2002)

Low power wireless sensor networks provide a new monitoring and control capability for civil and military applications in transportation, manufacturing, biomedical technology, environmental management, and safety and security systems. Low power integrated CMOS systems are being developed for microsensors, signal processors, microcontrollers, communication transceivers and network access control. This paper covers recent advances in CMOS-based microsensor systems, low power signal processing and RF communication circuits. Communication circuits include the demonstration of a 20 /spl mu/A supply current, 860 MHz, low phase noise CMOS local oscillator.
Oxidative DNA damage: mechanisms, mutation, and disease (2003)

Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.
Purification and characterization of dimethylsulfoniopropionate lyase from an alcaligenes-like dimethyl sulfide-producing marine isolate (1995)

Dimethyl sulfide (DMS) is quantitatively the most important biogenic sulfur compound emitted from oceans and salt marshes. It is formed primarily by the action of dimethylsulfoniopropionate (DMSP) lyase which cleaves DMSP, an algal osmolyte, to equimolar amounts of DMS and acrylate. This report is the first to describe the isolation and purification of DMSP lyase. The soluble enzyme was purified to electrophoretic homogeneity from a facultatively anaerobic gram-negative rod-shaped marine bacterium identified as an Alcaligenes species by the Vitek gram-negative identification method. The key to successful purification of the enzyme was its binding to, and hydrophobic chromatography on, a phenyl-Sepharose CL-4B column. DMSP lyase biosynthesis was induced by its substrate, DMSP; its product, acrylate; and also by acrylamide. The relative effectivenesses of the inducers were 100, 90, and 204%, respectively. DMSP lyase is a 48-kDa monomer with a Michaelis-Menten constant (K(infm)) for DMSP of 1.4 mM and a V(infmax) of 408 (mu)mol/min/mg of protein. It converted DMSP to DMS and acrylate stoichiometrically. The similar K(infm) values measured for pure DMSP lyase and the axenic culture, seawater, and surface marsh sediment suggest that the microbes in these ecosystems must have enzymes similar to the one purified from our marine isolate. Anoxic sediment populations, however, have a 40-fold-lower K(infm) for this enzyme (30 (mu)M), possibly giving them the capability to metabolize much lower levels of DMSP than the aerobes.
An improved method for isolation and culture of rat retinal pigment epithelial cells. (1985)

Retinal pigment epithelial cells from normal, Long Evans (LE) and retinal dystrophic (RCS) rats can be grown in vitro (Edwards, 1977). An improved technique is described which permits a more rapid isolation of RPE cells, and routinely gives high cell yields (30,000-40,000/eye), excellent cell viability (95%), and high plating efficiencies (95-100%). Whole eyes are treated with hyaluronidase and collagenase followed by trypsin. These enzymes degrade components of the extracellular matrix, releasing sheets of RPE from adherent attachments to the retina and choroid. Trypsin was then used to dissociate the sheets into single cells. RPE cells are grown to confluence in primary culture. This technique permits RPE cell isolation from both normal and retinal dystrophic (RCS) rats, 8-15 days of age. Normal cells isolated by this technique consistently show excellent phagocytosis in vitro.
Polyphosphate exerts differential effects on blood clotting, depending on polymer size (2010)

Polyphosphate, a linear polymer of inorganic phosphate, is secreted by activated platelets and accumulates in many infectious microorganisms. We recently showed that polyphosphate modulates the blood coagulation cascade at 3 steps: it triggers the contact pathway, it accelerates factor V activation, and it enhances fibrin polymerization. We now report that polyphosphate exerts differential effects on blood clotting, depending on polymer length. Very long polymers (≥ 500mers, such as those present in microorganisms) were required for optimal activation of the contact pathway, while shorter polymers (∼ 100mers, similar to the polymer lengths released by platelets) were sufficient to accelerate factor V activation and abrogate the anticoagulant function of the tissue factor pathway inhibitor. Optimal enhancement of fibrin clot turbidity by polyphosphate required ≥ 250mers. Pyrophosphate, which is also secreted by activated platelets, potently blocked polyphosphate-mediated enhancement of fibrin clot structure, suggesting that pyrophosphate is a novel regulator of fibrin function. In conclusion, polyphosphate of the size secreted by platelets is very efficient at accelerating blood clotting reactions but is less efficient at initiating them or at modulating clot structure. Microbial polyphosphate, which is highly procoagulant, may function in host responses to pathogens.
ARCBALL: A user interface for specifying three-dimensional orientation using a mouse (1992)

Arcball is an input technique for 3-D computer graphics, using a mouse to adjust the spatial orientation of an object. In Arcball, human factors and mathematical fundamentals come together exceptionally well. Arcball provides con-sistency between free and constrained rotations using any direction as an axis; consistent visual input and feedback; kinesthetic agreement between mouse motion and object rotation; and consistent interpretation of mouse position. Attention to mathematical detail facilitates the tasks of users and implementors. Users say that as a general-purpose rotation controller Arcball is easier to use than its nearest rival, the Virtual Sphere. It is also more powerful, and simpler to implement. Résumé Arcball est une interface utilisateur pour un système de visualisation 3D utilisant la souris pour orienter les objets dans l’espace. Dans Arcball, facteurs humains et concepts mathématiques se marient exceptionnellement bien. Arcball assure la consistence entre rotations libres et contraintes quelle que soit la direction de leur axe. Consistence entre l&amp;apos;entrée et la réponse; accord kinésique entre mouvements de la souris et rotations de l’objet; interprétation consistente des positions de la souris. Les utilisateurs affirment que le contrôleur universel de rotation Arcball est plus simple à utiliser que son concurent direct: «the Virtual Sphere». Il est aussi plus puissant et plus simple à implémenter. Key Words: object movement, view movement, mouse, user interface, interactive graphics, 3D graphics, rotation,
CORE-ANNULAR FLOWS (1997)

▪ Abstract This paper gives an overview of the issues posed by the science and technology of transporting heavy oils in a sheath of lubricating water. It touches on measures of energy efficiency, industrial experience, fouling, stability, models of levitation, and future directions.
Enzymatic Synthesis of a Bacterial Polyketide from Acetyl and Malonyl Coenzyme A (1993)

Microorganisms and plants manufacture a large collection of medically and commercially useful natural products called polyketides by a process that resembles fatty acid biosynthesis. Genetically engineered microorganisms with modified polyketide synthase (PKS) genes can produce new metabolites that may have new or improved pharmacological activity. A potentially general method to prepare cell-free systems for studying bacterial type II PKS enzymes has been developed that facilitates the purification and reconstitution of their constituent proteins. Selective expression of different combinations of the Streptomyces glaucescens tetracenomycin (Tcm) tcmJKLMN genes in a tcmGHIJKLMNO null background has been used to show that the Tcm PKS consists of at least the TcmKLMN proteins. Addition of the TcmJ protein to the latter four enzymes resulted in a greater than fourfold increase of overall activity and thus represents the optimal Tcm PKS. Polyclonal antibodies raised against each of the TcmKLMN proteins strongly inhibit the Tcm PKS, as do known inhibitors targeted to the active site Cys and Ser residues of a fatty acid synthase. This system exhibits a strict starter unit specificity because neither propionyl, butyryl, or isobutyryl coenzyme A substitute for acetyl coenzyme A in assembly of the Tcm decaketide. Because the Tcm PKS activity is significantly diminished by removal of the TcmM acyl carrier protein and can be restored by addition of separately purified TcmM to two different types of TcmM-deficient PKS, it should be possible to use such preparations to assay for each of the constituents of the Tcm PKS.
Class switch from μ to δ is mediated by homologous recombination between σμ and σμ sequences in human immunoglobulin gene loci (1989)

Class switch of immunoglobulin from mu to gamma occurs by recombination between two repetitive switch sequences: S mu and S gamma. However, there are no such sequences in the mu-delta introns of human and mouse genomes. Although the frequency of IgD-secreting cells is extremely low in mouse about 1% of patients with myeloma produce IgD in human. In a previous report (Nucleic Acids Res. 1988. 16: 9497) we reported that a 442-bp DNA sequence located in the JH-mu intron (defined as sigma mu) was inserted into the mu-delta intron (defined as sigma mu) in human genome. There is no such insertion in mouse. We analyzed Ig H chain gene loci of two human IgD myelomas: one was analyzed by cloning and sequencing and the other by Southern hybridization. We found that recombination had occurred between these two homologous DNA sequences, resulting in loss of the DNA segment from sigma mu to sigma mu. On the other hand, in a Burkitt lymphoma, Daudi, the DNA fragment from sigma mu to sigma mu was duplicated. These results suggest that homologous recombination between sigma mu and sigma mu sequences mediates class switch from mu to delta in human and that it occurs via unequal crossing-over between sister chromatids or daughter chromosomes.
OPTICAL PROPERTIES OF HUMAN BRAIN (1983)

Abstract— Optical properties of the human brain in the wave‐length region from blue to near infrared are presented. There are significant variations in the optical penetration depth from the neonatal and to the adult brain. Typical values for the penetration depth in the adult brain are: 0.5 mm for blue/green, 1.5 mm for red and 3.5 mm for near infrared. The values for the neonatal brain are typically 2–3 times larger.
Genetic analyses and molecular characterization of the pathways involved in the conversion of 2‐phenylethylamine and 2‐phenylethanol into phenylacetic acid in Pseudomonas putida U (2007)

In Pseudomonas putida U two different pathways (Pea, Ped) are required for the conversion of 2-phenylethylamine and 2-phenylethanol into phenylacetic acid. The 2-phenylethylamine pathway (PeaABCDEFGHR) catalyses the transport of this amine, its deamination to phenylacetaldehyde by a quinohaemoprotein amine dehydrogenase and the oxidation of this compound through a reaction catalysed by a phenylacetaldehyde dehydrogenase. Another catabolic route (PedS(1)R(1)ABCS(2)R(2)DEFGHI) is needed for the uptake of 2-phenylethanol and for its oxidation to phenylacetic acid via phenylacetaldehyde. This implies the participation of two different two-component signal-transducing systems, two quinoprotein alcohol dehydrogenases, a cytochrome c, a periplasmic binding protein, an aldehyde dehydrogenase, a pentapeptide repeat protein and an ABC efflux system. Additionally, two accessory sets of elements (PqqABCDEF and CcmABCDEFGHI) are necessary for the operation of the main pathways (Pea and Ped). PqqABCDEF is required for the biosynthesis of pyrroloquinoline quinone (PQQ), a prosthetic group of certain alcohol dehydrogenases that transfers electrons to an independent cytochrome c; whereas CcmABCDEFGHI is required for cytochrome c maturation. Our data show that the degradation of phenylethylamine and phenylethanol in P. putida U is quite different from that reported in Escherichia coli, and they demonstrate that PeaABCDEFGHR and PedS(1)R(1)ABCS(2)R(2)DEFGHI are two upper routes belonging to the phenylacetyl-CoA catabolon.
Automated synthesis of phase shifters for built-in self-test applications (2000)

This paper presents novel systematic design techniques for the automated register transfer level synthesis of phase shifters-circuits used to remove effects of structural dependencies featured by pseudorandom test pattern generators driving parallel scan chains. Using a concept of linear feedback shift register (LFSR) duality this paper relates the logical states of LFSRs and circuits spacing their inputs to each of the output channels. Consequently, the method generates a phase-shifter network satisfying criteria of channel separation and circuit complexity by taking advantage of simple logic simulation of the LFSRs. It is shown that it is possible to synthesize in a time-efficient manner very large and fast phase shifters for built-in self-test applications with guaranteed minimum phaseshifts between scan chains, and very low delay and area of virtually one two-way XOR gate/channel.
N-CAM in cerebrospinal fluid: a marker of synaptic remodelling after acute phases of multiple sclerosis? (1987)

We made a longitudinal study of the cerebrospinal fluid (CSF) neural cell adhesion molecule (N-CAM) content of 20 multiple sclerosis (MS) patients in an acute phase, and 10 in a non-acute phase. Both groups were compared with a control group of 23 subjects without neurological diseases. All MS patients were subjected to two or three lumbar punctures for collection of CSF samples, once a week. N-CAM analysis was performed by an enzyme-linked immunosorbent assay (ELISA) method. Comparison of N-CAM concentrations of the first CSF samples from each MS group with the control group values showed statistically different (lower) levels in the non-acute phase MS patients. Furthermore, a statistically significant increase of CSF N-CAM emerged from a comparison of the values of the first, second, and third samples of the acute phase MS patients group. This increase paralleled the patients' clinical improvement.
Effects of ligand binding on the association properties and conformation in solution of retinoic acid receptors RXR and RAR11Edited by M. F. Moody (2001)

In higher eukaryotes, vitamin A derived metabolites such as 9-cis and all-trans retinoic acid (RA), are involved in the regulation of several essential physiological processes. Their pleiotropic physiological effects are mediated through direct binding to cognate nuclear receptors RXRs and RARs that act as regulated transcription factors belonging to the superfamily of nuclear hormone receptors. Hormone binding to the structurally conserved ligand-binding domain (LBD) of these receptors triggers a conformational change that principally affects the conserved C-terminal transactivation helix H12 involved in transcriptional activation. We report an extensive biophysical solution study of RAR alpha, RXR alpha LBDs and their corresponding RXR alpha/RAR alpha LBD heterodimers combining analytical ultracentrifugation (AUC), small-angle X-ray and neutron scattering (SAXS and SANS) and ab initio three-dimensional shape reconstruction at low resolution. We show that the crystal structures of RXRs and RARs LBDs correlate well with the average conformations observed in solution. Furthermore we demonstrate the effects of 9-cisRA and all-transRA binding on the association properties and conformations of RXR alpha and RAR alpha LBDs in solution. The present study shows that in solution RAR alpha LBD behaves as a monomer in both unliganded and liganded forms. It confirms the existence in solution of a ligand-induced conformational change towards a more compact form of the LBD. It also confirms the stability of the predicted RXR alpha/RAR alpha LBD heterodimers in solution. SAS measurements performed on three different types of RXR alpha/RAR alpha LBD heterodimers (apo/apo, apo/holo and holo/holo) with respect to their ligand-binding site occupancy show the existence of three conformational states depending on the progressive binding of RA stereoisomers on RAR alpha and RXR alpha LBD subunits in the heterodimeric context. These results suggest that the subunits are structurally independent within the heterodimers. Our study also underlines the particular behaviour of RXR alpha LBD. In solution unliganded RXR alpha LBD is observed as two species that are unambiguously identified as homotetramers and homodimers. Molecular modelling combined with SAS data analysis allows us to propose a structural model for this autorepressed apo-tetramer. In contrast to the monomeric state observed in the crystal structure, our data show that in solution active holo-RXR alpha LBD bound to 9-cisRA is a homodimer regardless of the protein concentration. This study demonstrates the crucial role of ligands in the regulation of homodimeric versus heterodimeric association state of RXR in the NR signalling pathways.