gebhart/patrepeval huggingface dataset:
EXTENSIVE PROLONGATION OF RAT RENAL ALLOGRAFT SURVIVAL FOLLOWING DONOR OR NONSPECIFIC TRANSFUSIONS AND CONCOMITANT IMMUNOSUPPRESSANT1 (1987)

We report here a marked beneficial effect upon rat renal allograft survival transplanted across a strong histocompatibility barrier (BN----LEW) by pretransplant concomitant donor-strain blood transfusion (DST) and CsA treatment. Comparisons between recipient groups treated with pretransplant nonspecific blood (NST) and concomitant cyclosporine (CsA) or azathioprine (Aza) administration were also made. LEW recipients receiving only a BN renal allograft survived for a geometric average time of 8.9 days. Recipients receiving 1 ml of donor blood at weekly intervals, each week for three weeks prior to transplantation, demonstrated a geometric mean survival time (GMST) of 40.5 days. Recipients receiving this same regimen and concurrent CsA cover (5 mg/kg/day) starting 7 days prior to the first transfusion with discontinuation 5 days prior to transplantation showed extensive prolongation (greater than 100 days). Recipients treated with only CsA cover survived for a GMST of 34.4 days. LEW recipients receiving 1 ml of nonspecific blood at weekly intervals (DA, BUF, WKY, respectively) each week for 3 weeks prior to transplantation were prolonged to 27.7 days. Recipients treated with this same regimen while under CsA cover also demonstrated extended prolongation (greater than 100 days). Recipients receiving multiple donor blood transfusions under Aza (2 mg/kg/day) cover demonstrated lesser prolongation (22.8 days). Recipients receiving the multiple nonspecific blood protocol under Aza cover showed similar prolongation (38.6 days). Recipients treated only with Aza did not show prolonged survival (9.3 days). These differences in survival were considered significant among the 9 transplant groups as determined by ANOVA (P less than 0.001). The majority of recipient groups showed relatively poor renal function over their life spans, independent of whether prolongation occurred. Yet, renal function in the NST or particularly the DST groups covered by pretransplant CsA, demonstrated the best renal function in our laboratory over many years of investigations using the BN----LEW combination. In conclusion, there was a dramatic synergistic beneficial effect of prior multiple DST or NST specific to CsA, as opposed to another immunopharmacologic agent, Aza.
Heterogeneous levels of delta-like 4 within a multinucleated niche cell maintains muscle stem cell diversity (2022)

The quiescent muscle stem cell (QSC) pool is heterogeneous and generally characterized by the presence and levels of intrinsic myogenic transcription factors. Whether extrinsic factors maintain the diversity of states across the QSC pool remains unknown. The muscle fiber is a multinucleated syncytium that serves as a niche to QSCs, raising the possibility that the muscle fiber regulates the diversity of states across the QSC pool. Here, we show that the muscle fiber maintains a continuum of quiescent states, through a gradient of Notch ligand, Dll4, produced by the fiber and captured by QSCs. The abundance of Dll4 captured by the QSC correlates with the protein levels of the stem cell (SC) identity marker, Pax7. Niche-specific loss of Dll4 decreases QSC diversity and shifts the continuum to cell states that are biased toward more proliferative and committed fates. We reveal that fiber-derived Mindbomb1 (Mib1), an E3 ubiquitin ligase activates Dll4 and controls the heterogeneous levels of Dll4. In response to injury, with a Dll4-replenished niche, the normal continuum and diversity of the SC pool is restored, demonstrating bidirectionality within the SC continuum. Our data show that a post-translational mechanism controls heterogeneity of Notch ligands in a multinucleated niche cell to maintain a continuum of metastable states within the SC pool during tissue homeostasis.
Impact of guanidine-containing backbone linkages on stereopure antisense oligonucleotides in the CNS (2022)

Attaining sufficient tissue exposure at the site of action to achieve the desired pharmacodynamic effect on a target is an important determinant for any drug discovery program, and this can be particularly challenging for oligonucleotides in deep tissues of the CNS. Herein, we report the synthesis and impact of stereopure phosphoryl guanidine-containing backbone linkages (PN linkages) to oligonucleotides acting through an RNase H-mediated mechanism, using Malat1 and C9orf72 as benchmarks. We found that the incorporation of various types of PN linkages to a stereopure oligonucleotide backbone can increase potency of silencing in cultured neurons under free-uptake conditions 10-fold compared with similarly modified stereopure phosphorothioate (PS) and phosphodiester (PO)-based molecules. One of these backbone types, called PN-1, also yielded profound silencing benefits throughout the mouse brain and spinal cord at low doses, improving both the potency and durability of response, especially in difficult to reach brain tissues. Given these benefits in preclinical models, the incorporation of PN linkages into stereopure oligonucleotides with chimeric backbone modifications has the potential to render regions of the brain beyond the spinal cord more accessible to oligonucleotides and, consequently, may also expand the scope of neurological indications amenable to oligonucleotide therapeutics.
Effect of Antitubular Basement Membrane and Brush Border Antibodies on <i>p</i><i>-</i>Aminohippurate Transport in Kidney (1981)

Anti-TBM antibodies were associated with decreased slice uptake of PAH-3H while anti-BB antibodies were associated with decreased luminal PAH secretion in vitro and in vivo.
Lithium salts — Simple but magic (2014)

For many decades pharmacological drugs based on lithium salts have been successfully used in psychiatry to treat bipolar disorder, and they remain the "gold standard" of pharmacological therapy of patients with this disease. At the same time, over recent years in experiments in vitro and in vivo a plethora of evidence has accumulated on a positive effect of lithium ions in other areas including their neuro-, cardio-, and nephroprotective properties, regulation of stem cells functions, regulation of inflammation, and others. Numerous studies have shown that the effect of lithium ions involves several mechanisms; however, one of its main targets in the implementation of most of the effects is glycogen synthase kinase 3β, a key enzyme in various pathological and protective signaling pathways in cells. However, one of the main limitations of the use of lithium salts in clinics is their narrow therapeutic window, and the risk of toxic side effects. This review presents the diversity of effects of lithium ions on the organism emphasizing their potential clinical applications with minimal undesirable side effects. In the end, we present a schematic "Lithiometer", comparing the range of Li(+) concentrations that might be used for the treatment of acute pathologies with possible toxic effects of Li(+).
Segmental migration of the hindbrain neural crest does not arise from its segmental generation (1993)

The proposed pathways of chick cranial neural crest migration and their relationship to the rhombomeres of the hindbrain have been somewhat controversial, with differing results emerging from grafting and DiI-labelling analyses. To resolve this discrepancy, we have examined cranial neural crest migratory pathways using the combination of neurofilament immunocytochemistry, which recognizes early hindbrain neural crest cells, and labelling with the vital dye, DiI. Neurofilament-positive cells with the appearance of premigratory and early-migrating neural crest cells were noted at all axial levels of the hindbrain. At slightly later stages, neural crest cell migration in this region appeared segmented, with no neural crest cells obvious in the mesenchyme lateral to rhombomere 3 (r3) and between the neural tube and the otic vesicle lateral to r5. Focal injections of DiI at the levels of r3 and r5 demonstrated that both of these rhombomeres generated neural crest cells. The segmental distribution of neural crest cells resulted from the DiI-labelled cells that originated in r3 and r5 deviating rostrally or caudally and failing to enter the adjacent preotic mesoderm or otic vesicle region. The observation that neural crest cells originating from r3 and r5 avoided specific neighboring domains raises the intriguing possibility that, as in the trunk, extrinsic factors play a major role in the axial patterning of the cranial neural crest and the neural crest-derived peripheral nervous system.
The H3antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers (2013)

ABT-288 was tolerated at a 15-fold higher dose and 12-fold higher exposures in subjects with schizophrenia than previously observed in healthy volunteers. The greater ABT-288 tolerability was not due to limited brain uptake.
Advanced turbine design for coal-fueled engines (1992)

The objective of this task is to perform a technical assessment of turbine blading for advanced second generation PFBC conditions, identify specific problems/issues, and recommend an approach for solving any problems identified. A literature search was conducted, problems associated with hot corrosion defined and limited experiments performed. Sulfidation corrosion occurs in industrial, marine and aircraft gas turbine engines and is due to the presence of condensed alkali (sodium) sulfates. The principle source of the alkali in industrial, marine and aircraft gas turbine engines is sea salt crystals. The principle source of the sulfur is not the liquid fuels, but the same ocean born crystals. Moreover deposition of the corrosive salt occurs primarily by a non-equilibrium process. Sodium will be present in the cleaned combusted gases that enter the PFBC turbine. Although equilibrium condensation is not favored, deposition via impaction is probable. Marine gas turbines operate in sodium chloride rich environments without experiencing the accelerated attack noted in coal fired boilers where condensed chlorides contact metallic surfaces. The sulfates of calcium and magnesium are the products of the reactions used to control sulfur. Based upon industrial gas turbine experience and laboratory tests, calcium and magnesium sulfates are, at temperatures up to 1500[degrees]F (815[degrees]C), relatively innocuous salts. In this study it is found that at 1650[degrees]F (900[degrees]C) and above, calcium sulfate becomes an aggressive corrodent.
Epigenetic Determinants of Cancer (2016)

SUMMARYEpigenetic changes are present in all human cancers and are now known to cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin. Cancer genetics and epigenetics are inextricably linked in generating the malignant phenotype; epigenetic changes can cause mutations in genes, and, conversely, mutations are frequently observed in genes that modify the epigenome. Epigenetic therapies, in which the goal is to reverse these changes, are now one standard of care for a preleukemic disorder and form of lymphoma. The application of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route.
An Unusual Domino Retro‐Ene—Conia Reaction: Regio‐ and Stereoselective One‐Carbon Ring Expansion of Fenchol Derivatives. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Ion Atmosphere Relaxation Control of Electron Transfer Dynamics in a Plasticized Carbon Dioxide Redox Polyether Melt (2003)

The sorption of CO(2) into the highly viscous, semisolid hybrid redox polyether melt, [Co(phenanthroline)(3)](MePEG-SO(3))(2), where MePEG-SO(3) is a MW 350 polyether-tailed sulfonate anion, remarkably accelerates charge transport in this molten salt material. Electrochemical measurements show that as CO(2) pressure is increased from 0 to 800 psi (54 atm) at 23 degrees C, the physical diffusion coefficient D(PHYS) of the Co(II) species, the rate constant k(EX) for Co(II/I) electron self-exchange, and the physical diffusion coefficient of the counterion D(COUNTERION) all increase, from 4.3 x 10(-10) to 6.4 x 10(-9) cm(2)/s, 4.1 x 10(6) to 1.6 x 10(7) M(-1) s(-1), and 3.3 x 10(-9) to 1.6 x 10(-8) cm(2)/s, respectively. Plots of log(k(EX)) versus log(D(PHYS)) and of log(k(EX)) versus log(D(COUNTERION)) are linear, showing that electron self-exchange rate constants are closely associated with processes that also govern D(PHYS) and D(COUNTERION). Slopes of the plots are 0.68 and 0.98, respectively, indicating a better linear correlation between k(EX) and D(COUNTERION). The evidence indicates that k(EX) can be controlled by relaxation of the counterion atmosphere about the Co complexes in the semisolid redox polyether melts. Because the counterion relaxation is in turn controlled by polyether "solvent" fluctuations, this is a new form of solvent dynamics control of electron transfer.
PHYTOHEMAGGLUTININ MITOGENIC PROTEINS (1973)

The phytohemagglutinin (PHAP) glycoproteins derived from Phaseolus vulgaris consist of five isomitogens that are tetrameric structures made up of two different glycoprotein subunits. Although identical in size (mol wt = 34,000), the subunits differ in their isoelectric points and amino acid sequences for six of the first seven amino-terminal residues, but are identical in primary structure from the 8th through the 24th amino acid residue. The isomitogen containing four L subunits (L-PHAP) is a potent leukoagglutinin and mitogen that lacks hemagglutinating properties. The isomitogen made up of four R subunits (4R H-PHAP) is a potent hemagglutinin. The hybrid isomitogens consisting of varying proportions of the two subunits (3L-1R, 2L-2R, 1L-3R) are capable of causing mixed erythrocyte-lymphocyte agglutination. These studies provide a structural basis for explaining the differences in biological activities of the various PHAP isomitogens.
Bilayered phospholipid micelles and capillary electrophoresis: A new additive for electrokinetic chromatography (2003)

Phospholipid micelles and bilayered micelles (bicelles) were investigated as a new media for electrokinetic chromatography. The benefit to using these additives for micellar electrokinetic chromatography (MEKC) is the potential of a simple bilayer membrane model operated with fast analysis time, and low sample injection volumes. The system is used to separate peptides/protein and is tested with a series of beta-blockers. The results suggest that bicelle electrokinetic chromatography provides selectivity and holds potential as an alternative approach to modeling membrane phenomenon.
Quantitative Analysis of Low-Field NMR Signals in the Time Domain (2001)

Two novel methods are described for direct quantitative analysis of NMR free induction decay (FID) signals. The methods use adaptations of the generalized rank annihilation method (GRAM) and the direct exponential curve resolution algorithm (DECRA). With FID-GRAM, the Hankel matrix of the sample signal is compared with that of a reference mixture to obtain quantitative data about the components. With FID-DECRA, a single-sample FID matrix is split into two matrices, allowing quantitative recovery of decay constants and the individual signals in the FID. Inaccurate results were obtained with FID-GRAM when there were differences between the frequency or transverse relaxation time of signals for the reference and test samples. This problem does not arise with FID-DECRA, because comparison with a reference signal is unnecessary. Application of FID-DECRA to 19F NMR data, which contained overlapping signals from three components, gave concentrations comparable to those derived from partial least squares (PLS) analysis of the Fourier transformed spectra. However, the main advantage of FID-DECRA was that accurate (<5% error) and precise (2.3% RSD) results were obtained using only one calibration sample, whereas with PLS, a training set of 10 standard mixtures was used to give comparable accuracy and precision.
Influence of compressive biaxial strain on the hydrogen uptakeof ultrathin single-crystal vanadium layers (1997)

We have investigated the influence of biaxial compressive strain on the thermodynamic properties of hydrogen in thin, single-crystal vanadium layers (0.9, 1.6, and 2.0 nm). At H/V0.1 (atomic ratio), the host-mediated H-H interaction was found to be attractive. For H/V&gt;0.1, the interaction was found to be extremely weak in the 0.9-nm-thick layer and repulsive in the 1.6- and 2.0-nm-thick V layers. The repulsive interaction was found to increase with increasing layer thicknesses. These results are unexpected as the interaction is attractive in both bulk V and in thin vanadium layers under biaxial tensile strain for H/V0.5. Both the strained and unstrained vanadium lattices are found to have roughly the same hydrogen affinity at H/V=0.1 (0.3 eV/H). No ordered bulklike \ensuremath{\mathrm{B}} phase was observed at any concentration (0/V\ensuremath{\leqslant}1) in the temperature range 30--250t\ifmmode^\circ\else\textdegree\fi{}C. Methods used in this study are resistivity measurements, x-ray diffraction, and nuclear reaction analysis.
Diagnosis of carotid artery disease: preliminary experience with maximum-intensity-projection spiral CT angiography. (1993)

Our results show that spiral CT angiography shows normal and abnormal carotid anatomy well when compared with conventional angiography. The short examination time and clear depiction of arterial caliber in areas of stenosis are significant advantages of spiral CT angiography compared with MR angiography.
Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle (2017)

The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs. The fourth safety study conducted in 10 lactating cows using an AdtA24 vaccine serial showed that the vaccine was completely absent from milk. The fifth safety study was conducted under typical U.S. production field conditions in 500 healthy beef and dairy cattle using two AdtA24 vaccine serials. These results demonstrated that the vaccine was safe when used per the product label recommendations. Additional data collected during these five studies confirmed that AdtA24 vaccinees developed FMDV A24 and the HAd5 vaccine vector serum neutralization antibodies that test negative in a FMDV non-structural protein antibody test, confirming AdtA24 vaccine's capability to differentiate infected from vaccinated animals (DIVA). In conclusion, results from this comprehensive set of cattle studies demonstrated the safety of the replication-deficient AdtA24 vaccine and fulfilled safety-related requirements for U.S. regulatory requirements.
Reliability issues in advanced High k/metal gate stacks for 45 nm CMOS applications (2006)

Some recent insights in reliability issues of high k/metal gate stacks for the 45 nm CMOS node and beyond are discussed. The problem of transient charging effects leading to threshold voltage instability is illustrated. It is shown that nitridation of Hf-silicate layers leads to severe degradation of the negative-bias-instability (NBTI) lifetime. Some insights in the mechanisms of time-dependent-dielectric breakdown (TDDB) are discussed and illustrated
Kinematic error correction for minimally invasive surgical robots (2004)

Robots are useful tools in minimally invasive surgery, providing benefits such as reduction in hand tremor, navigation, and workspace scaling. Unfortunately, minimally invasive configurations result in two likely sources of kinematic error: port displacement and instrument shaft flexion. For a quasistatic system, a measure is presented that relates the errors in the robot Jacobian to the angular difference between desired motions and actual motions. Simulations and experimental data demonstrate this measure for a laboratory system. One potential use for the presented measure is, for bounded errors, determining whether the system monotonically converges for all initial and desired positions in the workspace. In addition, the measure is useful for path planning, determining less error-prone paths.
A Method for Estimating Mileage Improvement and Emission Reductions Achievable by Hybrid-Electric Vehicles (1975)

The results of two derivations relating to the fuel economy of hybrid-electric vehicles (vehicles which employ both a heat engine and electric drive system) are presented and their use is illustrated through the examples of the University of Wisconsin and TRW Systems Group hybrid-electric vehicles. The method of mileage estimation employs a specific fuel-consumption versus torque-speed map for the heat engine under study and knowledge of the hybrid-vehicle dynamics and road-load power. The method is easily extended to estimation of emission reductions through use of specific-emission- production versus torque-speed maps and is applicable to hybrid vehicles with other than electrical energy- storage systems.
Supplementary Figures 1-13 from A c-Myc Activation Sensor-Based High-Throughput Drug Screening Identifies an Antineoplastic Effect of Nitazoxanide (2023)

&lt;p&gt;PDF file - 1.5 MB, Fig. S1. Scheme of the c-Myc activation sensor; Fig. S2. Optimal cell plating numbers for HTS format; Fig. S3. Optimal substrate concentration and imaging time for HTS format; Fig. S4. Robustness of the cell assay; Fig. S5. Plot of the occurrence frequency of compound classes for all the clean hits from five libraries; Fig. S6. The percent inhibition at 10�M of all the clean hits from the NCC library and the IC50 of all the clean hits from the Lopac library are plotted; Fig. S7. Plot of IC50 of all the clean hits from combined MS, BMI and BMF libraries; Fig. S8. The top three unexpected potent hits. The chemical structures of the three most potent hits that were not previously described to have an inhibitory effect on c-Myc are shown; Fig. S9A. Western blot analysis of lymphoma and sarcoma cells after NTZ treatment was performed using phospho c-Myc, c-Myc protein and �-actin antibodies; Fig. S9B. Dose dependent inhibition of phospho c-Myc by NTZ in different cancer cell lines; Fig. S10. Effect of NTZ on cell viability; Fig. S11. In vivo efficacy of NTZ in a SK-FST xenograft model; Fig. S12. Plot of the average body weight of NTZ or CMC treated group at indicated days after implantation.&lt;/p&gt;
Reconstruction of surface potential from Kelvin probe force microscopy images (2013)

We present an algorithm for reconstructing a sample surface potential from its Kelvin probe force microscopy (KPFM) image. The measured KPFM image is a weighted average of the surface potential underneath the tip apex due to the long-range electrostatic forces. We model the KPFM measurement by a linear shift-invariant system where the impulse response is the point spread function (PSF). By calculating the PSF of the KPFM probe (tip+cantilever) and using the measured noise statistics, we deconvolve the measured KPFM image to obtain the surface potential of the sample.The reconstruction algorithm is applied to measurements of CdS-PbS nanorods measured in amplitude modulation KPFM (AM-KPFM) and to graphene layers measured in frequency modulation KPFM (FM-KPFM). We show that in the AM-KPFM measurements the averaging effect is substantial, whereas in the FM-KPFM measurements the averaging effect is negligible.