gebhart/patrepeval huggingface dataset:
Induction of Steady‐State Blood Alcohol Levels: Application to the Study of Within‐Session Alcohol Tolerance in Rats (2001)

The continuous alcohol infusion procedure (alcohol clamp) maintained BAC in a steady state, both within and between subjects, across a wide range of blood alcohol levels. The alcohol clamp appears to be a useful tool for subsequent studies of within-session alcohol tolerance in the rat.
Protective anti-tumour immune responses by murine dendritic cells pulsed with recombinant Tat-carcinoembryonic antigen derived from Escherichia coli (2009)

Carcinoembryonic antigen (CEA) is over-expressed on various human cancer cells and has been the target of immunotherapies using dendritic cells (DCs) pulsed with CEA-specific RNA or peptides, or transduced by CEA-expressing adenovirus or vaccinia virus. Because activated DCs do not phagocytose soluble protein antigens efficiently and pure immature DCs are not obtained easily ex vivo, an efficacious whole CEA protein-loaded DC vaccine has not been reported. To improve the antigen delivery into DCs, we utilized CEA conjugated to a protein-transduction domain, human immunodeficiency virus transactivating Tat. Furthermore, we purified the truncated non-glycosylated CEA from Escherichia coli to overcome the safety concerns and immunosuppressive functions associated with the native CEA protein. Using confocal microscopy and fluorescence activating cell sorter analysis, we demonstrated that the Tat-CEA protein entered the cytoplasm of DCs efficiently within 10 min of co-culture, compared with the negligible amount of CEA into DCs 30 min later. CEA-specific T cell proliferation and cytotoxic T cell responses were enhanced significantly in mice immunized with Tat-CEA-pulsed DCs [DC (Tat-CEA)] compared with those immunized with CEA-pulsed DCs [DC (CEA)]. T helper type 1 responses were more prominent in the DC (Tat-CEA) immunized mice whose splenocytes secreted more interferon-gamma and less interleukin-4 than those from DC (CEA) immunized mice. In vivo, the DC (Tat-CEA) vaccine delayed tumour growth significantly and prolonged survival of tumour-bearing mice. These results suggest that protective epitopes are well preserved on bacteria-derived recombinant Tat-CEA. This strategy may provide a basic platform for DC-based anti-CEA vaccines that could be utilized in combination with advanced immune-enhancing therapeutics.
Different Glycosylation Requirements for the Synthesis of Enzymatically Active Angiotensin-converting Enzyme in Mammalian Cells and Yeast (1996)

For facilitating crystallization and structural studies of the testicular isozyme of angiotensin-converting enzyme (ACE,), we attempted the production of enzymatically active ACET proteins which are unglycosylated or underglycosylated. Expression in Escherichia coli of the rabbit ACET cDNA resulted in the synthesis of an unglycosylated but inactive protein. Similarly, unglycosylated ACET synthesized in HeLa cells, by using a cDNA in which all five potential N-glycosylation sites had been mutated, was inactive and rapidly degraded. Several ACET variants carrying mutations in one or more of the potential N-glycosylation sites were used to examine the role of glycosylation at specific sites on ACET synthesis, transport to the cell surface, cleavage processing, and enzyme activity. These experiments demonstrated that allowing glycosylation only at the first or the second site, as counted from the NH2 terminus, was sufficient for normal synthesis and processing of active ACET. In contrast, ACETg3, which had only the third glycosylation site available, was unglycosylated, enzymatically inactive and rapidly degraded. N-Glycosylated ACET could also be produced in yeast. Surprisingly, the mutant ACETg3 was synthesized, N-glycosylated, and properly transported in yeast. Wild type and mutant ACE proteins were cleavage-secreted from yeast and enzymatically active.
A CHROMOSOME REPLICATION PATTERN DEDUCED FROM PERICARP PHENOTYPES RESULTING FROM MOVEMENTS OF THE TRANSPOSABLE ELEMENT, MODULATOR, IN MAIZE (1984)

Modulator (Mp) was mapped after it transposed from the P locus on chromosome 1 by studying 105 light variegated/red twin sectors on medium variegated pericarp ears. Sixty-one percent of the receptor sites were detectably linked to P, and these showed an asymmetry of distribution adjacent to P. No transpositions were mapped in the 4 map units proximal to P, whereas 23 cases mapped to the same length distal to P. The remaining transpositions of Mp on chromosome 1, both proximal and distal to P, were equally scattered. It has previously been shown that when Modulator transposes it replicates at the P locus and a second time at the receptor site. The pattern of transposition adjacent to P is consistent with a hypothesis that a replicon initiation site is situated proximal to P; that Modulator transposes at the time of replication; that it is not able to transpose into a replicated region but only into a replicating one. No difference in distribution of receptor sites was found when the Modulator was detected vs. not detected in the red co-twins by testing with a Dissociation element.
Performance Characteristics of Metal Mesh Foil Bearings: Predictions Versus Measurements (2013)

Proven low-cost gas bearing technologies are sought to enable more compact rotating machinery products with extended maintenance intervals. The paper presents an analysis for predicting the static and dynamic forced performance characteristics of metal mesh foil bearings (MMFBs) which comprise a top foil supported on a layer of metal mesh of a certain compactness. The analysis couples a finite element model of the top foil and underspring support with the gas film Reynolds equation. A comparison of the predictions against laboratory measurements with two bearings aims to validate the analysis. The predicted drag friction factor in one bearing (L = D = 28.00 mm) during full film operation is just f ∼ 0.03 at ∼50,000 rpm, in good agreement with measurements at increasing applied loads. The predictions further elucidate the effect of the applied load and rotor speed on the bearing minimum film thickness, journal eccentricity, and attitude angle. For a second bearing (L = 38.0 mm, D = 36.5 mm), predicted bearing force coefficients show magnitudes comparable with the measurements, with less than a 20% difference, in the 250–350 Hz excitation frequency range. While the predicted direct stiffness coefficients are rather constant, the experimental force coefficients increase with frequency (maximum 400 Hz), due mainly to the increasing amplitudes of dynamic force applied to excite the bearing with a set amplitude of motion. The analysis underpredicts the direct damping coefficients at high frequencies (&gt;300 Hz). The cross-coupled stiffness and damping coefficients are typically lower (&lt;40%) than the direct ones. The bearings operated stably at all speeds without any subsynchronous whirl. The reasonable agreement of the predictions with the available test data promote the better design and further development of MMFB supported rotating machinery.
Ectopic expression of carcinoembryonic antigen by a melanoma cell leads to changes in the transcription of two additional cell adhesion molecules. (1995)

Ectopic expression of carcinoembryonic antigen (CEA) by the melanoma cell line Mel Wei led to alterations in cell morphology and to changes in the expression of two melanoma-associated cell adhesion molecules, neural cell adhesion molecule and MUC18. The normally flat, triangular cells developed neurite-like extensions and exhibited a less organized growth pattern. When compared to untransfected Mel Wei cells or to those transfected with an irrelevant cDNA, two independent CEA transfectants showed a decrease in the expression of neural cell adhesion molecule and an increase in the expression of MUC18. These changes, which are characteristic of the metastatic phenotype in melanomas, were observed at the cell surface and at the level of mRNA and were independent of adherent growth. Steady-state levels of neural cell adhesion molecule mRNA were reduced in CEA-expressing cells by approximately 5-fold, while MUC18 mRNA showed an 8-fold increase. No significant differences in the expression of intercellular adhesion molecule-1 or beta-2 microglobulin were observed between Mel Wei and CEA-Mel Wei. These data indicate that changes in the expression of a single cell adhesion molecule such as CEA can lead to alterations in the expression of unrelated cell adhesion molecules and may contribute to the general derangement of adhesive interactions observed frequently in tumor cells.
Design and Synthesis of a Fluoroindolocarbazole Series as Selective Topoisomerase I Active Agents. Discovery of Water-Soluble 3,9-Difluoro-12,13-dihydro-13-[6-amino-β- d-glucopyranosyl]-5H,13H-benzo[b]- thienyl[2,3-a]pyrrolo[3,4-c]carbazole- 5,7(6H)-dione (BMS-251873) with Curative Antitumor Activity against Prostate Carcinoma Xenograft Tumor Model (2004)

A series of fluoroindolocarbazoles were studied with respect to their topoisomerase I activity, cytotoxicity, selectivity, and in vivo antitumor activity. Emerging from this series was BMS-251873, a potential clinical candidate possessing a robust pharmacological profile including curative antitumor activity against prostate carcinoma.
Translational Fusions with Fragments of the trpE Gene Improve the Expression of a Poorly Expressed Heterologous Gene in Escherichia coli (1989)

A series of plasmids expressing fusions between the trpE gene product, anthranilate synthase component I and the major immunogen (VP1) of foot and mouth disease virus were constructed such that increasing amounts of the 3' end of trpE were deleted. Deletions removing up to 70% of trpE had little effect on the quantity of fusion protein expressed, while the number of molecules appeared to increase. Larger deletions led to a steady decrease in both the quantity of fusion protein produced and in the number of molecules. This is consistent with trpE being responsible for the high levels of expression of VP1 by its gene product stabilizing VP1 against proteolytic degradation. Some out-of-frame deletion mutants were also produced. All deletion mutants in one wrong reading frame expressed low levels of two VP1-containing polypeptides. This observation is interpreted as being due to re-initiation of translation at a site inside the VP1 sequence which is activated by local termination of translation.
Dynamic Modulation of Chemical Concentration in an Aqueous Droplet (2007)

The shrinkage factor: Chemical and biological processes are governed by the frequency of molecular collisions, which are dictated by the concentration of the dissolved species. Dynamic control over the concentrations of dissolved species in a nanoscale reaction vessel (droplet; colored pink in the picture) provides a new degree of control that will aid in the study of fundamental chemical processes.
Anterior cervical interbody fusion with hydroxyapatite graft and plate system (2001)

Hydroxyapatite grafts are very efficient in achieving cervical fusion, maintaining intervertebral disc height, and restoring lordosis. When combined with the placement of a cervical plate, immediate stability is achieved and graft displacement is prevented.
Risks of Transthoracic Needle Biopsy (2012)

Transthoracic needle lung biopsy is a commonly performed diagnostic procedure for pulmonary nodules and masses. To make an informed decision about whether to pursue this procedure, doctors and patients must be aware of the possible risks of the procedure. We performed a MEDLINE search, 2003-2012 to identify relevant English-language studies that included at least 100 subjects and reported data on complications of transthoracic needle lung biopsy performed within the last 10 years. We found the most common complication to be any pneumothorax (risk 15-25%), with pneumothorax requiring chest tube occurring less often (risk 4-6%). Hemorrhage, defined as radiographically visualized blood along the needle tract was common, but clinically significant hemorrhage was infrequent (~1%). Rare complications, including air embolism and tumor seeding of the biopsy tract, occurred in fewer than 1% of cases but were potentially serious. We summarize data on factors associated with complications, including patient age, COPD, lesion size and location, and number of punctures. We also provide data on techniques to mitigate severity of pneumothorax post-biopsy, such as rapid patient rollover, manual aspiration, and instillation of substances into the biopsy tract.
Rational Design of a Potent, Long-Lasting Form of Interferon:  A 40 kDa Branched Polyethylene Glycol-Conjugated Interferon α-2a for the Treatment of Hepatitis C (2001)

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.
Photochemical Treatment with S-59 Psoralen and Ultraviolet A Light to Control the Fate of Naive or Primed T Lymphocytes In Vivo After Allogeneic Bone Marrow Transplantation (1999)

Donor leukocyte infusions after allogeneic bone marrow transplantation can provide a curative graft-vs-leukemia (GVL) effect, but there is a significant risk of graft-vs-host (GVH) disease. A simple and effective method for controlling the fate of naive or primed T-lymphocytes in vivo without eliminating their beneficial properties is needed. In this report, photochemical treatment (PCT) ex vivo with a synthetic psoralen (S-59) and UVA light was evaluated as a pharmacological approach to limiting the proliferation and GVH potential of naive and primed donor T cells in vivo. S-59 rapidly intercalates into and cross-links DNA on UVA illumination. The effects of PCT on T cells were found to be both S-59 and UVA dose dependent. With selected PCT regimens, treated T cells still expressed activation markers (CD25 and CD69) and secreted IL-2 on activation, but they showed limited proliferative capacity in vitro and in vivo. Clonal expansion of CTL in MLR was reduced after PCT, but short term lytic activity of primed CTL was not affected. In a murine model of MHC-mismatched bone marrow transplantation, the addition of PCT-treated T cells to T-depleted bone marrow facilitated donor engraftment and complete chimerism without causing acute or chronic graft-vs-host disease. Allospecific GVL reactivity was reduced but not eliminated after PCT treatment. In an MHC-matched model using host-presensitized donor T cells, PCT significantly reduced GVH-associated mortality without eliminating GVL reactivity. Thus, PCT ex vivo offers a simple, rapid, and inexpensive method by which to control the fate of naive and primed T cells in vivo.
Improvements to combinational equivalence checking (2006)

The paper explores several ways to improve the speed and capacity of combinational equivalence checking based on Boolean satisfiability (SAT). State-of-the-art methods use simulation and BDD/SAT sweeping on the input side (i.e. proving equivalence of some internal nodes in a topological order), interleaved with attempts to run SAT on the output (i.e. proving equivalence of the output to constant 0). This paper improves on this method by (a) using more intelligent simulation, (b) using CNF-based SAT with circuit-based decision heuristics, and (c) interleaving SAT with low-effort logic synthesis. Experimental results on public and industrial benchmarks demonstrate substantial reductions in runtime, compared to the current methods. In several cases, the new solver succeeded in solving previously unsolved problems.
A mutation in sigma‐1 receptor causes juvenile amyotrophic lateral sclerosis (2011)

Sigma-1 receptors are known to have neuroprotective properties, and recently Sigmar1 knockout mice have been described to have motor deficiency. Our findings emphasize the role of sigma-1 receptors in motor neuron function and disease.
AlfvÉnic Accelerated Electrons And Short Burst Auroral Kilometric Radiations Observed By The Fast Satellite (2007)

This investigation is motivated by previous study of short burst radiations (S-bursts) reported by Ergun et al. [2006], who suggested two generation mechanisms of S-bursts: one is the electron cyclotron maser instability due to an unstable ring distribution; the other is an upward electron beam generating upper hybrid resonance. The simulation results reported by Su et al. [2007] support the former mechanism. Only one Earth-based S-burst event was reported prior to our study. A systematic study was performed on particle and field observations from the FAST spacecraft to search for events of S-bursts and Alfvén waves. Eight events involving coexistence were identified and are presented in this thesis. All of them were observed at altitudes greater than 2500 km during winter months. In addition, S-bursts associated with Alfvénic perturbations were detected during periods when the AE indices were high, indicating a possible association with substorms. Furthermore, 24 dayside Alfvénic events and 20 nightside events were examined in detail. We found that the electron phase space density peaks along the magnetic field line for the nightside, which supports the concept of field-aligned acceleration by inertial Alfvén waves. However, the electron anisotropies involving the phase space densities peaked perpendicular to the magnetic field were observed on the dayside.
Neutral endopeptidase inhibition and the natriuretic peptide system: an evolving strategy in cardiovascular therapeutics (2012)

Hypertension and heart failure (HF) are common diseases that, despite advances in medical therapy, continue to be associated with high morbidity and mortality. Therefore, innovative therapeutic strategies are needed. Inhibition of the neutral endopeptidase (NEPinh) had been investigated as a potential novel therapeutic approach because of its ability to increase the plasma concentrations of the natriuretic peptides (NPs). Indeed, the NPs have potent natriuretic and vasodilator properties, inhibit the activity of the renin-angiotensin-aldosterone system, lower sympathetic drive, and have antiproliferative and antihypertrophic effects. Such potentially beneficial effects can be theoretically achieved by the use of NEPinh. However, studies have shown that NEPinh alone does not result in clinically meaningful blood pressure-lowering actions. More recently, NEPinh has been used in combination with other cardiovascular agents, such as angiotensin-converting enzyme inhibitors, and antagonists of the angiotensin receptor. Another future possible combination would be the use of NEPinh with NPs or their newly developed chimeric peptides. This review summarizes the current knowledge of the use and effects of NEPinh alone or in combination with other therapeutic agents for the treatment of human cardiovascular disease such as HF and hypertension.
Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. (1995)

Infection of adherent primary monocytes with HIV-1Ba-L is significantly suppressed in the presence of human saliva. By reverse transcriptase (RT) levels, saliva, although present for only 1 h during monocyte viral exposure, inhibited HIV-1 infectivity for 3 wk after infection, whereas human plasma and synovial fluid failed to inhibit HIV-1 infectivity. Antiviral activity was identified in the saliva soluble fraction, and to determine the factor(s) responsible, individual saliva proteins were examined. Of those proteins examined, only secretory leukocyte protease inhibitor (SLPI) was found to possess anti-HIV-1 activity at physiological concentrations. SLPI anti-HIV-1 activity was dose dependent, with maximal inhibition at 1-10 micrograms/ml (> 90% inhibition of RT activity). SLPI also partially inhibited HIV-1IIIB infection in proliferating human T cells. SLPI appears to target a host cell-associated molecule, since no interaction with viral proteins could be demonstrated. However, SLPI anti-HIV-1 activity was not due to direct interaction with or downregulation of the CD4 antigen. Partial depletion of SLPI in whole saliva resulted in decreased anti-HIV-1 activity of saliva. These data indicate that SLPI has antiretroviral activity and may contribute to the important antiviral activity of saliva associated with the infrequent oral transmission of HIV-1.
Functional Flexibility of the FimH Adhesin: Insights from a Random Mutant Library (2000)

Type 1 fimbriae are surface organelles of Escherichia coli which mediate D-mannose-sensitive binding to different host surfaces. This binding is conferred by the minor fimbrial component FimH. Naturally occurring variants of the FimH protein have been selected in nature for their ability to recognize specific receptor targets. In particular, variants that bind strongly to terminally exposed monomannose residues have been associated with a pathogenicity-adaptive phenotype that enhances E. coli colonization of extraintestinal locations such as the urinary bladder. In this study we have used random mutagenesis to specifically identify nonselective mutations in the FimH adhesin which modify its binding phenotype. Isogenic E. coli clones expressing FimH variants were tested for their ability to bind yeast cells and model glycoproteins that contain oligosaccharide moieties rich in either terminal monomannose, oligomannose, or nonmannose residues. Both the monomannose- and the oligomannose-binding capacity of type 1 fimbriae could be altered by minor amino acid changes in the FimH protein. The monomannose-binding phenotype was particularly sensitive to changes, with extensive differences in binding being observed in comparison to wild-type FimH levels. Different structural alterations were able to cause similar functional changes in FimH, suggesting a high degree of flexibility to target recognition by this adhesin. Alteration of residue P49 of the mature FimH protein, which occurs within the recently elucidated carbohydrate-binding pocket of FimH, completely abolished its function. Amino acid changes that increased the binding capacity of FimH were located outside receptor-interacting residues, indicating that functional changes relevant to pathogenicity are likely to be due to conformational changes of the adhesin.