gebhart/patrepeval huggingface dataset:
Conferring RNA polymerase Activity to a DNA polymerase: A single residue in reverse transcriptase controls substrate selection (1997)

The traditional classification of nucleic acid polymerases as either DNA or RNA polymerases is based, in large part, on their fundamental preference for the incorporation of either deoxyribonucleotides or ribonucleotides during chain elongation. The refined structure determination of Moloney murine leukemia virus reverse transcriptase, a strict DNA polymerase, recently allowed the prediction that a single amino acid residue at the active site might be responsible for the discrimination against the 2'OH group of an incoming ribonucleotide. Mutation of this residue resulted in a variant enzyme now capable of acting as an RNA polymerase. In marked contrast to the wild-type enzyme, the K(m) of the mutant enzyme for ribonucleotides was comparable to that for deoxyribonucleotides. The results are consistent with proposals of a common evolutionary origin for both classes of enzymes and support models of a common mechanism of nucleic acid synthesis underlying catalysis by all such polymerases.
The Pathophysiology of the Anterior Tibial Compartment Syndrome (1978)

In an experimental study in dogs of the anterior tibial compartment syndrome, three measurements were taken before, during, and following raising pressure in the compartment: blood flow, muscle function, and peroneal nerve conduction. If fasciotomy was performed within 4 hours, peroneal nerve conduction velocity always returned to normal regardless of amount of pressure or length of time pressure was applied; if performed after 12 hours peroneal nerve conduction velocity did not return to normal at any pressure or time condition, suggesting that irreversible damage to the nerve had occurred. Blood flow, as measured by rate of clearance of Xe133, always returned to normal within 2 hours of fasciotomy regardless of the time postinjury or amount of pressure applied. Muscle function (CPK and LDH) did not always return to baseline with fasciotomy and in some instances the absolute values were higher after fasciotomy. Further clinical studies using these measurements are recommended.
A simple procedure for tenascin purification (1992)

Here we describe a two-step procedure for purification of human tenascin from conditioned medium of the SK-MEL-28 human melanoma cell line. The first step consists in passing the conditioned media through two chromatography columns connected in sequence. The first is a large capacity gelatin--Sepharose affinity chromatography column (to remove fibronectin), the second, over which the unbound material from the first column flows directly, is a hydroxyapatite chromatography column. Under these conditions, all tenascin present in the conditioned medium binds to the hydroxyapatite chromatography column from which it is then eluted by a 5-300 mM sodium phosphate gradient. With this step, we obtain a crude tenascin preparation, concentrated about 20 times with respect to the starting conditioned medium, and in which tenascin represents more than 50% of the total protein. The second step consists of two sequential precipitations with 6% and 12.8% poly(ethylene glycol). After this step, tenascin is more than 95% pure and does not show any contamination of chondroitin-sulfate-containing proteoglycans that are known to bind to it. From 21 medium we obtain about 3-4 mg tenascin which corresponds to a yield of about 40-50%. This procedure gives a higher yield, is simpler with respect to procedures previously described, avoids the exposure of the protein to denaturing agents or harsh conditions and could be used for purification of tenascin from the conditioned media of other cell lines. Thus, this procedure may represent a simple and useful tool for the preparation of tenascin to study its biological functions.
Convolution surfaces (1991)

Smoothly blended articulated models are often difficult to construct using current techniques. Our solution in this paper is to extend the surfaces introduced by Blinn [Blinn 1982] by using three-dimensional convolution with skeletons composed of polygons or curves. The resulting convolution surfaces permit fluid topology changes, seamless part joins, and efficient implementation.
Coaxing HIV-1 from resting CD4 T cells (2004)

With advances in antiretroviral therapy, HIV infection might be cleared by intensive time-limited treatment coupled with practical strategies that disrupt latency without enhancing new infection. HDAC inhibitors are capable of inducing expression of quiescent provirus, without fully activating cells or enhancing de novo infection, and may be useful in future clinical protocols that seek to eradicate HIV infection.
Synchrocyclotron Improvement Programs (1969)

A number of groups are engaged in improvement of synchrocyclotrons in order to increase beam current and improve extraction efficiency and beam precision. This paper reviews the major problems involved in such improvements and the solutions contemplated by the several groups. Goals are beams of 10μa or more with extraction efficiency of at least 50% and a tenfold gain in spatial and energy definition of the beams.
Effect of Out-of-Band Blockers on the Required Linearity, Phase Noise, and Harmonic Rejection of SDR Receivers Without Input SAW Filter (2018)

The required linearity of wideband receivers for applications, such as software-defined radio in the absence of input surface-acoustic wave (SAW) filters, is studied. It is shown that the required linearity of wideband SAW-less receivers is surprisingly higher than what has been commonly assumed. For these receivers, although the out-of-band blockers can reduce the compression point of the receiver, they can also potentially generate interferers that appear in the desired frequency band, resulting in higher noise floor and signal corruption. The required out-of-band IIP2 and IIP3 of low-noise amplifier (LNA) and mixer for single and concurrent applications are analytically derived. The required wideband SAW-less receiver phase noise is also studied, and it is shown that blockers located at the frequencies of the local oscillator harmonics can significantly increase the noise floor of the receiver. The effects of input and intermediate filters on the above applications along with the conditions under which they help to alleviate the limitations of LNA and mixer are defined. The validity of the models and subsequent derivations is verified by actual measurements using a wideband SAW-less receiver.
Clinical-Scale Production of CAR-T Cells for the Treatment of Melanoma Patients by mRNA Transfection of a CSPG4-Specific CAR under Full GMP Compliance (2019)

Chimeric antigen receptor (CAR)-T cells already showed impressive clinical regressions in leukemia and lymphoma. However, the development of CAR-T cells against solid tumors lags behind. Here we present the clinical-scale production of CAR-T cells for the treatment of melanoma under full GMP compliance. In this approach a CAR, specific for chondroitin sulfate proteoglycan 4 (CSPG4) is intentionally transiently expressed by mRNA electroporation for safety reasons. The clinical-scale protocol was optimized for: (i) expansion of T cells, (ii) electroporation efficiency, (iii) viability, (iv) cryopreservation, and (v) potency. Four consistency runs resulted in CAR-T cells in clinically sufficient numbers, i.e., 2.4 × 10<sup>9</sup> CAR-expressing T cells, starting from 1.77x10<sup>8</sup> PBMCs, with an average expansion of 13.6x, an electroporation efficiency of 88.0% CAR-positive cells, a survival of 74.1% after electroporation, and a viability of 84% after cryopreservation. Purity was 98.7% CD3<sup>+</sup> cells, with 78.1% CD3<sup>+</sup>/CD8<sup>+</sup> T cells and with minor contaminations of 1.2% NK cells and 0.6% B cells. The resulting CAR-T cells were tested for cytolytic activity after cryopreservation and showed antigen-specific and very efficient lysis of tumor cells. Although our work is descriptive rather than investigative in nature, we expect that providing this clinically applicable protocol to generate sufficient numbers of mRNA-transfected CAR-T cells will help in moving the field of adoptive cell therapy of cancer forward.
Role of the mevalonate pathway of isoprenoid synthesis in IL-8 generation by activated monocytic cells (1994)

The highly regulated enzyme HMG-CoA reductase generates mevalonate, the precursor of a complex series of isoprenoids that posttranslationally modify (isoprenylate) certain proteins (e.g., the low-molecular-weight GTP-binding proteins) or that are incorporated into cholesterol and other end products. We recently reported that isoprenoids are required for NADPH oxidase activity in granulocytes via LMW GTP-binding protein isoprenylation. In this study, we evaluated the effects of isoprenoid depletion on the expression of proinflammatory genes in human monocytic THP-1 cells. We selected conditions under which pretreatment for 24 h with isoprenoid synthesis inhibitors (HMG-CoA reductase inhibitor lovastatin or compactin at 10 microM) did not compromise cell viability but markedly suppressed H2O2 generation. Under these conditions interleukin-8 (IL-8) production was attenuated (by 50-90%) in response to lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, and phorbol myristate acetate. Coincubation of reductase inhibitor-treated cells with mevalonate prevented the attenuation of IL-8 production by reductase inhibitors. The effects of isoprenoid depletion on cytokine production were selective: IL-1 beta generation was not inhibited but the production of IL-6 and IL-8 was concomitantly suppressed. IL-8 induction was suppressed at least in part through attenuation of the increase in mRNA in stimulated cells. We conclude that isoprenoid generation through the mevalonate pathway is a requirement for IL-8 induction by activated monocytic cells in vitro. Isoprenylation inhibitors have the potential to alter monocyte proinflammatory function.
Eosinophils express interleukin 5 and granulocyte macrophage-colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics. (1992)

IL-5 and granulocyte macrophage-colony-stimulating factor (GM-CSF) are important regulators of eosinophil survival, proliferation, and effector function. To determine whether IL-5 and/or GM-CSF are generated by eosinophils at sites of allergic inflammation, we have used in situ hybridization with 35S-labeled RNA probes to study the expression of IL-5 and GM-CSF mRNA in bronchoalveolar lavage (BAL) eosinophils derived from asthmatics (n = 5) before and after endobronchial allergen challenge. Endobronchial allergen challenge induced a significant airway eosinophilia (pre-allergen challenge 0.6 +/- 0.5% eosinophilia vs post-allergen challenge 48.2 +/- 25.6% eosinophilia). Post-allergen challenge eosinophils expressed IL-5 and GM-CSF mRNA, but did not express IL-1 beta or IL-2 mRNA. To determine whether the IL-5 mRNA-positive cells coexpressed GM-CSF mRNA, double mRNA labeling experiments with a digoxigenin-11-UTP nonradioactive labeled IL-5 RNA probe and a GM-CSF 35S-labeled RNA probe were performed. These studies demonstrated that individual eosinophils expressed one of four cytokine mRNA profiles (IL-5+, GM-CSF+, 34 +/- 13%; IL-5+, GM-CSF-, 34 +/- 5%; IL-5-, GM-CSF+, 11 +/- 9%; IL-5-, GM-CSF-, 21 +/- 25%). The expression of IL-5 and GM-CSF by eosinophils at sites of allergic inflammation in asthmatics may provide an important autocrine pathway, maintaining the viability and effector function of the recruited eosinophils.
Structural Investigation of the Metallic Glasses Mg85.5Cu14.5 and Mg70Zn30 (1983)

Abstract The total structure factors as well as the total pair correlation functions for amorphous Mg 85.5 Cu 14.5 (by neutron and X-ray diffraction) and for amorphous Mg 70 Zn 30 (by X-ray diffraction) were determined. Both alloys show similar chemical short range order effects. From the total pair correlation function of the Mg 85.5 Cu 14.5 glass, partial coordination numbers and atomic distances could be extracted. Comparison with the structure of crystalline Mg 2 Cu suggests that the short range order around the copper atoms is similar in the amorphous and the crystalline phase. The densities of both amorphous alloys were measured yielding negative excess volumina.
Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcγRIIB (CD32B) (2012)

Fc receptors (FcRs) play a key role in regulating and coordinating responses from both innate and adaptive arms of the immune system. The inhibitory Fc gamma receptor II (FcγRIIB; CD32) is central to this regulation with FcγRIIB(-/-) mice demonstrating augmented responses to mAb immunotherapy, elevated incidence and severity of auto-immunity, and increased response to mAb-mediated cancer therapy. To date, these observations have remained unexploited therapeutically, partly through a lack of specific mAb reagents capable of exclusively binding mouse FcγRIIB. Thus almost all of the FcγRIIB-binding mAb currently available, such as 2.4G2, also bind FcγRIII (CD16), and polyclonal reagents have limited availability and are of unproven specificity and avidity, making in vivo manipulation of FcγRIIB impossible. Following an extensive immunisation protocol using FcγRIIB(-/-) mice, we recently produced three unique mAb that are suitable for this purpose. Here we characterise these novel reagents and demonstrate that they fall into two distinct categories; those which cause phosphorylation and subsequent activation of FcγRIIB (agonistic) and those that block receptor phosphorylation (antagonistic). These two types of mAb exhibit different characteristics in a range of biochemical, cellular, and functional assays relevant to FcγRIIB activity and mAb therapy.
The Natural History of Progression From Normal Glucose Tolerance to Type 2 Diabetes in the Baltimore Longitudinal Study of Aging (2003)

The natural history of progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is not well defined. We studied this progression using biennial oral glucose tolerance tests performed in the Baltimore Longitudinal Study of Aging and survival analysis to assess progression from NGT to abnormal fasting plasma glucose (FPG; > or =6.1 mmol/l), abnormal 2-h plasma glucose (2hPG; > or =7.8 mmol/l), IFG (FPG 6.1-6.9 mmol/l, 2hPG < or =7.8 mmol/l), and IGT (FPG <6.1 mmol/l, 2hPG 7.8-11.0 mmol/l), and from IFG-IGT to diabetes (FPG > or =7.0 mmol/l or 2hPG > or =11.1 mmol/l). At baseline, the 815 subjects had a mean age of 57 years, 35% were women, and 60% had NGT. Of the 488 subjects with NGT, over half were followed for at least 10 years. By 10 years, 14% had progressed to abnormal FPG and 48% to abnormal 2hPG. Of the 267 subjects who progressed to IFG-IGT, 216 had additional follow-up. By 10 years, 8% of these progressed to diabetes by FPG whereas 27% progressed by 2hPG. In subsidiary analyses, we defined "abnormal" FPG as > or =5.55 mmol/l and "diabetic" FPG as > or =6.1 mmol/l, making the baseline prevalence of IFG similar to that of IGT. By these criteria, 43% progressed to abnormal FPG and 43% to abnormal 2hPG by 10 years of follow-up; among subjects developing impaired FPG or 2hPG, 22% progressed to diabetes by FPG whereas 17% progressed by 2hPG at 10 years. Nonetheless, 42% of subjects developing abnormal FPG did not develop abnormal 2hPG, and vice versa. We conclude that, although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural histories in the evolution of type 2 diabetes.
Facile, Efficient Routes to Diverse Protected Thiols and to Their Deprotection and Addition to Create Functional Polymers by Thiol−Ene Coupling (2008)

Carbazole, dinitrobenzoate, phenol, pyridine, and 4-cyano-4‘-alkoxybiphenyl side groups were grafted onto pendant vinyl groups of polybutadiene (PB) by thiol−ene addition to yield functional polymer of polydispersity equal to that of the precursor material. Synthesis protocols that are clean (&gt;90% conversion to desired product) and scalable were developed to incorporate a protected thiol group into functional precursors. The resulting acetyl or benzoyl thioesters are suitable for long-term storage, and are conveniently deprotected and added to polymer in a matter of hours in a straightforward procedure that does not require isolation of the thiol intermediate. Alternatively, PB functionalization could be achieved with equal success by reaction with β-mercaptoethanol (BME), and subsequent esterification of the incorporated hydroxyl groups with a suitable acyl halide. The chemistry described can potentially be applied to add any side group onto any polymer, copolymer, or block copolymer displaying pendant vinyl groups.
Excited-state interconversion between emissive MLCT levels in a dinuclear Ru(ii) complex containing a bridging ligand with an extended π system (2000)

For a diruthenium complex, charge migration between different moieties of a bridging ligand with extended conjugation is directly monitored for the first time by using time-resolved emission and absorption spectroscopy.
Synaptic Efficacy Enhanced by Glial Cells in Vitro (1997)

In the developing nervous system, glial cells guide axons to their target areas, but it is unknown whether they help neurons to establish functional synaptic connections. The role of glial cells in synapse formation and function was studied in cultures of purified neurons from the rat central nervous system. In glia-free cultures, retinal ganglion cells formed synapses with normal ultrastructure but displayed little spontaneous synaptic activity and high failure rates in evoked synaptic transmission. In cocultures with neuroglia, the frequency and amplitude of spontaneous postsynaptic currents were potentiated by 70-fold and 5-fold, respectively, and fewer transmission failures occurred. Glial cells increased the action potential-independent quantal release by 12-fold without affecting neuronal survival. Thus, developing neurons in culture form inefficient synapses that require glial signals to become fully functional.
Low latency directional filtering for inter-layer prediction in scalable video coding using HEVC (2013)

In scalable video coding, reconstructed base-layer samples can be used as predictor for compressing enhancement-layer samples. This inter-layer predictor typically exhibits specific type of artifacts, arising from coarse quantization and upsampling processes. To suppress these artifacts, we propose an inter-layer filtering scheme which adapts to local orientations. On a sample-by-sample basis, it first determines the orientation class by comparing simple gradient measurements. According to the determined orientation, a corresponding directional filter constructed with predetermined coefficients, is selected and then applied. Our filtering scheme achieves low encoding latency and also avoids complicated normalization processes typically associated with other low-latency filtering methods. Based on complexity analysis and simulation results, we demonstrate that, compared with other inter-later filtering approaches, our method provides a viable complexity-efficiency trade-off for practical scalable video applications.
Organic thin-film transistor-driven polymer-dispersed liquid crystal displays on flexible polymeric substrates (2002)

We have fabricated organic thin-film transistor (OTFT)-driven active matrix liquid crystal displays on flexible polymeric substrates. These small displays have 16×16 pixel polymer-dispersed liquid crystal arrays addressed by pentacene active layer OTFTs. The displays were fabricated using a low-temperature process (&amp;lt;110 °C) on flexible polyethylene naphthalate film and are operated as reflective active matrix displays.
Electrocatalytic Carbon Dioxide Activation: The Rate‐Determining Step of Pyridinium‐Catalyzed CO2 Reduction (2011)

The reactivity of reduced pyridinium with CO(2) was investigated as a function of catalyst concentration, temperature, and pressure at platinum electrodes. Concentration experiments show that the catalytic current measured by cyclic voltammetry increases linearly with pyridinium and CO(2) concentrations; this indicates that the rate-determining step is first order in both. The formation of a carbamate intermediate is supported by the data presented. Increased electron density at the pyridyl nitrogen upon reduction, as calculated by DFT, favors a Lewis acid/base interaction between the nitrogen and the CO(2). The rate of the known side reaction, pyridinium coupling to form hydrogen, does not vary over the temperature range investigated and had a rate constant of 2.5 M(-1) s(-1). CO(2) reduction followed Arrhenius behavior and the activation energy determined by electrochemical simulation was (69±10) kJ mol(-1).
Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy (2019)

Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)-derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy <i>in vitro</i>. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs. SIGNIFICANCE: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. <i>In vitro</i> drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.<i>See related commentary by Hill and D'Andrea, p. 828</i>.<i>This article is highlighted in the In This Issue feature, p. 813</i>.