gebhart/patrepeval huggingface dataset:
Magnetic and electrochemical studies on Ni2+-substituted Li–Mn spinel oxides (2005)

Li Mn 2 − x Ni x O 4 ( x &amp;lt; 0.5 ) cubic spinel oxide was synthesized by the sol-gel technique using Li-nitrate, Mn-acetate, and Ni-acetate salts. The gel precursors were decomposed at 300°C in air and then annealed at temperatures ranging from 500to850°C in an oxygen flow. For a fixed annealing temperature of 700°C, the lattice constant linearly decreased with an increase in the substitution degree x. As x increased, the low-temperature magnetization increased and the asymptotic Curie temperature moved in the positive direction and changed its sign from negative to positive around x=0.2. Additionally, the redox capacity of 4.7V plateau was increased at the expense of the capacity around 4.0V. When the x value was fixed at 0.5, all the specimens showed ferromagnetic magnetization. The minimum lattice parameter, the maximum Curie temperature, and the maximum magnetization were attained simultaneously for the specimen annealed at 700°C, which exhibited only a plateau around 4.7V. It was possible to explain these variations by considering the magnetic interactions between transition-metal ions.
Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy (2017)

Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1. In addition, because the Epstein-Barr virus (EBV) residing in some CHL tumors is strongly immunogenic, we hypothesized that characteristics of the tumor immune microenvironment in EBV<sup>+</sup> CHL would be distinct from EBV<sup>-</sup> CHL, with specific implications for designing combination treatment regimens. Employing immunohistochemistry for immune cell subsets and checkpoint molecules, as well as gene expression profiling, we characterized 32 CHLs from the Johns Hopkins archives, including 12 EBV<sup>+</sup> and 20 EBV<sup>-</sup> tumors. Our results revealed a dichotomous cellular and cytokine immune milieu in EBV<sup>+</sup> vs EBV<sup>-</sup> CHL. EBV<sup>+</sup> tumors displayed a T helper 1 (Th1) profile typical of effective antitumor immunity, with increased infiltration of CD8<sup>+</sup> T cells and coordinate expression of the canonical Th1 transcription factor Tbet (<i>TBX21</i>), interferon-γ (<i>IFNG</i>), and the IFN-γ-inducible immunosuppressive enzyme indoleamine 2,3-dioxygenase. In contrast, EBV<sup>-</sup> tumors manifested a pathogenic Th17 profile and ongoing engagement of the interleukin-23 (IL-23)/IL-17 axis, with heightened phosphorylated signal transducer and activator of transcription 3 expression in infiltrating lymphocytes. These findings suggest that drugs blocking the IL-23/IL-17 axis, which are already in the clinic for treating certain autoimmune disorders, may enhance the therapeutic impact of anti-PD-1 therapy in EBV<sup>-</sup> CHL.
How MHC Class II Molecules Acquire Peptide Cargo: Biosynthesis and Trafficking through the Endocytic Pathway (1995)

The antigen-specific receptors of T lymphocytes rely on products of the major histocompatibility complex (MHC) to recognize and engage antigen. MHC molecules display antigen on the cell surface in the form of small peptides, generated intracellularly by fragmentation of the intact protein antigen. They acquire these peptides at distinct intracellular locations: In the endoplasmic reticulum (ER), class I molecules bind peptides derived from cytosolic proteins, whereas class II molecules acquire their peptide cargo in an endocytic compartment. Sequestration of class II molecules from the constitutive secretory pathway is mediated by their interaction with an additional polypeptide, the invariant chain (Ii). The Ii contains sorting signals in its cytoplasmic tail that target class II molecules to the endocytic pathway where they encounter peptides generated from protein antigens that have also accessed this route.
An Estoppel Doctrine for Patented Standards - eScholarship (2008)

Technical standards, such as interface protocols or file formats, are extremely important in the “network industries” that add so much value to the world economy today. Under some circumstances, the assertion of patent rights against established industry standards can seriously disrupt these network industries. We have in mind two particularly disruptive tactics: (1) the “snake in the grass,” whereby a patentee intentionally keeps a patent “quiet” while a standard is being designed or adopted, and then later, after the standard is entrenched, asserts the patent widely in an attempt to capitalize on its popularity; (2) the “bait and switch” ploy where a patentee encourages adoption by offering royaltyfree use of standard-related patents, and then, after the standard has gone into widespread use, begins to enforce its patents against adopters of the standard. We propose to counteract these tactics with a simple solution: over time, adopters of a standard ought to build up a “reliance interest” in the standard. Under our approach—which we call “standards estoppel”—non-assertion of a patent right in the presence of widespread adoption should create immunity from patent infringement. The fundamental idea behind this doctrine is to prevent “strategic” assertions of patents that exploit the logic of network “lock-in.” As we explain, though this is a simple doctrine based on deeply held common law principles, various gaps in the current doctrinal structure make this a necessary addition to the contemporary legal arsenal. In particular, “standards estoppel” plugs some dangerous conceptual holes in current rules relating to laches, waiver, estoppel, implied licensing, and patent misuse/antitrust. With this modest addition to the doctrinal fabric, patent law can more effectively guard against the risk of illegitimate leverage, thus more effectively fostering innovation in network industries.
Biomaterial engineered electrodes for bioelectronics (2000)

A series of single-cysteine-containing cytochrome c, Cyt c, heme proteins including the wild-type Cyt c (from Saccharomyces cereisiae) and the mutants (V33C, Q21C, R18C, G1C, K9C and K4C) exhibit direct electrical contact with Au-electrodes upon covalent attachment to a maleimide monolayer associated with the electrode. With the G1C–Cyt c mutant, which includes the cysteine residue in the polypeptide chain at position 1, the potential-induced switchable control of the interfacial electron transfer was observed. This heme protein includes a positively charged protein periphery that surrounds the attachment site and faces the electrode surface. Biasing of the electrode at a negative potential (−0.3 V s. SCE) attracts the reduced Fe(II)-Cyt c heme protein to the electrode surface. Upon the application of a double-potential-step chronoamperometric signal onto the electrode, where the electrode potential is switched to +0.3 V and back to −0.3 V, the kinetics of the transient cathodic current, corresponding to the re-reduction of the Fe(III)-Cyt c, is controlled by the time interval between the oxidative and reductive potential steps. While a short time interval results in a rapid interfacial electron-transfer, ket1=20 s−1, long time intervals lead to a slow interfacial electron transfer to the Fe(III)-Cyt c, ket2=1.5 s−1. The fast interfacial electron-transfer rate-constant is attributed to the reduction of the surface-attracted Fe(III)-Cyt c. The slow interfacial electron-transfer rate constant is attributed to the electrostatic repulsion of the positively charged Cyt c from the electrode surface, resulting in long-range electron transfer exhibiting a lower rate constant. At intermediate time intervals between the oxidative and reductive steps, two populations of Cyt c, consisting of surface-attracted and surface-repelled heme proteins, are observed. Crosslinking of a layered affinity complex between the Cyt c and cytochrome oxidase, COx, on an Au-electrode yields an electrically-contacted, integrated, electrode for the four-electron reduction of O2 to water. Kinetic analysis reveals that the rate-limiting step in the bioelectrocatalytic reduction of O2 by the integrated Cyt c/COx electrode is the primary electron transfer from the electrode support to the Cyt c units.
The Virtual Circular Genome Model for Primordial RNA Replication (2020)

Our manuscript describes a hypothesis for the replication of primordial RNA genomes by entirely nonenzymatic processes. Our proposal circumvents long standing problems such as the difficulty of copying long templates by nonenzymatic chemistry, the need for defined primers, and the so-called ‘last base addition problem’. Our hypothesis leads to surprising predictions, notably that the replication of an ensemble of oligonucleotides could be mediated by the template-directed extension of all oligos by as little as one nucleotide, on average. We propose experimental tests of our model, and discuss its implications for the origin of life.
Occurrence, finger printing and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in the Chenab River, Pakistan (2011)

Seventeen polycyclic aromatic hydrocarbons (PAHs) were studied in surface waters (including particulate phase) from the Chenab River, Pakistan and ranged from 289-994 and 437-1290 ng l(-1) in summer and winter (2007-09), respectively. Concentrations for different ring-number PAHs followed the trend: 3-rings > 2-rings > 4-rings > 5-rings > 6-rings. The possible sources of PAHs are identified by calculating the indicative ratios; appropriating petrogenic sources of PAHs in urban and sub-urban regions with pyrogenic sources in agricultural region. Factor analysis based on principal component analysis identified the origins of PAHs from industrial activities, coal and trash burning in agricultural areas and municipal waste disposal from surrounding urban and sub-urban areas via open drains into the riverine ecosystem. Water quality guidelines and toxic equivalent factors highlighted the potential risk of low molecular weight PAHs to the aquatic life of the Chenab River. The flux estimated for PAHs contaminants from the Chenab River to the Indus River was >50 tons/year.
Phase 1 clinical trial of chimeric monoclonal anti‐CD4 antibody in multiple sclerosis (1994)

We conducted an open trial of cM-T412, a chimeric monoclonal anti-CD4 antibody, in 29 patients with MS. This antibody caused a prompt and long-lasting depletion of circulating CD4 (helper/inducer) lymphocytes. The mean (+/- SE) CD4 count for the group decreased from 870 (+/- 66) cells/mm3 at baseline to 76 (+/- 11) 3 hours after treatment, and then increased to 425 (+/- 38) at 1 month after treatment and 475 (+/- 39) at 6 months after treatment. Numbers of CD8 (cytotoxic/suppressor) lymphocytes, B lymphocytes, granulocytes, and monocytes changed transiently but showed no significant long-term effects. The most common side effects were headache, nausea, myalgia, fever, and tachycardia occurring in the first few hours after treatment. No serious or unexpected infections or other significant adverse effects occurred. Kurtzke EDSS scores remained stable, and MRI scans showed less contrast enhancement 1 week after treatment. We conclude that treatment of MS patients with cM-T412 chimeric anti-CD4 antibody is well tolerated at the doses tested and produces a long-lasting, selective depletion of CD4 lymphocytes.
Compressible Dynamics of Cavitating 3-D Multi-Phase Flows (2009)

The aim of this research is to model and analyze compressible 3-D cavitating liquid flows with special emphasis on the detection of shock formation and propagation. For that purpose the 3-D compressible finite volume flow solver CATUM (CAvitation Technische Universität München) is developed, which enables the simulation of unsteady 3-D liquid flows with phase transition at all Mach numbers. The phase transition is modeled according to the equilibrium thermodynamics. The CFD tool CATUM is applied to highly unsteady two-phase flows inside fuel injection systems and to the flow around hydrofoils. The time dependent development of vapor clouds, their shedding mechanism and the resulting unsteady variation of flow variables are discussed in detail and compared with experimental results.
Positron Emission Tomography, Enzymes and Drug Research and Development (1993)

The use of Positron Emission Tomography (PET) to examine drug pharmacokinetics and pharmacodynamics and the relationship of these properties to the behavioral, therapeutic and toxic properties of drugs is emerging as a powerful new scientific tool (Fowler et al., 1990). PET provides a new perspective on drug research by virtue of its ability to directly assess different parameters such as absolute uptake, regional distribution, kinetics, pharmacological profile and metabolic effects of drugs in human subjects. For example, the labeled drug itself can be used to measure the absolute uptake, regional distribution and kinetics at its site of action in the body. Additionally, the labeled drug and whole body PET can be used to determine the target organs for the drug and its labeled metabolites, thus providing information on potential toxic effects as well as tissue half-lives. On the other hand, different labeled tracers can be used to assess the effects of a drug on particular physiological or functional processes. For example, with appropriate radiotracers, the effects of a drug on metabolism, neurotransmitter activity, blood flow, enzyme activity or other processes can be probed. Because of the short half-life of the positron emitters, these parameters can be assessed directly in the human body both in normal controls and in patients and serial studies can be done where a subject serves as his own control.
L’apport de nouvelles technologies dans la rééducation motrice et cognitive des patients cérébro-lésés (2017)

Suite à une lésion cérébrale, les troubles moteurs et cognitifs sont fréquents et leur rééducation constitue un réel défi pour les patients et les thérapeutes. Ces dernières années, la robotique et les jeux sérieux se sont fortement développés dans ce domaine afin d’augmenter la récupération fonctionnelle des patients. La robotique permet d’intensifier la thérapie, d’assister le mouvement du patient et de lui fournir un feedback. Quant aux jeux sérieux, ils rendent la rééducation ludique et motivante et le niveau de difficulté du jeu s’adapte continuellement aux performances du patient. Ces deux technologies complémentaires sont donc prometteuses dans la rééducation de patients cérébro-lésés.
The monomeric polypeptide comprises the functional flavanone 3β‐hydroxylase from Petunia hybrida (2000)

Flavanone 3beta-hydroxylase catalyzes the Fe(II)/oxoglutarate-dependent hydroxylation of (2S)-flavanones to (2R,3R)-dihydroflavonols in the biosynthesis of flavonoids, catechins and anthocyanidins. The enzyme had been partially purified from Petunia hybrida and proposed to be active as a dimer of roughly 75 kDa in size. More recently, the Petunia 3beta-hydroxylase was cloned and shown to be encoded in a 41655 Da polypeptide. In order to characterize the molecular composition, the enzyme was expressed in a highly active state in Escherichia coli and purified to apparent homogeneity. Size exclusion chromatographies of the pure, recombinant enzyme revealed that this flavanone 3beta-hydroxylase exists in functional monomeric and oligomeric forms. Protein cross-linking experiments employing a specific homobifunctional sulfhydryl group reagent or the photochemical activation of tryptophan residues confirmed the tendency of the enzyme to aggregate to oligomeric complexes in solution. Thorough equilibrium sedimentation analyses, however, revealed a molecular mass of 39. 2+/-12 kDa for the recombinant flavanone 3beta-hydroxylase. The result implies that the monomeric polypeptide comprises the catalytically active flavanone 3beta-hydroxylase of P. hybrida, which may readily associate in vivo with other proteins.
Diagnostic significance of free salivary testosterone measurement using a direct luminescence immunoassay in healthy men and in patients with disorders of androgenic status (2006)

The accurate measurement of testosterone remains a challenge. The determination of the blood testosterone concentrations in serum by conventional immunoassays is inaccurate in men and even more so in females and children. A new luminescence enzyme immunoassay (LIA) has been developed and validated. The high analytical (8.7 pmol/L) and functional (17.3 pmol/L) sensitivity allows the quantification of the very low concentration in saliva, as well as in serum, after 1/40 dilution. This study measured salivary testosterone levels and compared the results with the free levels calculated from total testosterone and sex hormone-binding globulin in eugonadal and hypogonadal men. Salivary testosterone concentrations in healthy men in morning hours were 369 pmol/L (mean), range 263-544 pmol/L, which was statistically significantly higher than that in men with androgen deficiency, 215 pmol/L (mean), range 51-249 pmol/L. Repetitive determination of free testosterone concentrations in saliva (once a week for 5 weeks) showed high stability of results over time, with coefficient of variation 9% (range 5-23%). In this study we showed that free salivary testosterone levels in morning samples correlated well with calculated free testosterone in blood, both in healthy men (R = 0.754, P = 0.001), and in patients with androgen deficiency (R = 0.889, P = 0.0001), though in cases with very low testosterone, salivary concentrations were systematically higher than calculated free testosterone levels in blood.
Pharmacokinetics of Dextromethorphan After Single or Multiple Dosing in Combination With Quinidine in Extensive and Poor Metabolizers (2004)

Dextromethorphan (DM) pharmacological properties predict that the widely used cough suppressant could be used to treat several neuronal disorders, but it is rapidly metabolized after oral dosing. To find out whether quinidine (Q), a CYP2D6 inhibitor, could elevate and prolong DM plasma profiles, 2 multiple-dose studies identified the lowest oral dose of Q that could be used in a fixed combination with 3 doses of DM. A multiple-dose study in healthy subjects with an extensive or a poor enzyme metabolizer phenotype evaluated the safety and pharmacokinetic profile of a selected fixed-dose combination (AVP-923). Study 1 randomized 46 healthy subjects, who were extensive CYP2D6 metabolizers, to receive 0, 2.5, 10, 25, 50, or 75 mg Q twice daily in combination with 30 mg DM for 7 days. Plasma and urine samples were collected after the first and last doses for the assay of DM, dextrorphan (DX), and Q. Study 2 randomized 65 healthy extensive CYP2D6 metabolizers to 8 groups given twice-daily 45- or 60-mg DM doses combined with 0, 30, 45, or 60 mg Q for 7 days. The effects of increasing Q were not different with doses greater than 25 mg, whereas lower doses showed a dose-related increase in plasma DM concentrations. Urinary ratios of DM/DX showed a Q dose- and time-related increase in the number of subjects converted to the poor metabolizer phenotype that reached 100% on day 3 of dosing with 25 mg Q. Results from both studies indicated that 25 to 30 mg Q is adequate to maximally suppress O-demethylation of DM. Study 3 evaluated 7 extensive metabolizers and 2 poor metabolizers given an oral capsule every 12 hours containing 30 mg Q combined with 30 mg DM. DM plasma AUC values increased in both groups of subjects during the 8-day study. The mean urinary metabolic ratio (DM/DX) increased at least 27-fold in extensive metabolizers by day 8. There was no effect of Q on urinary metabolic ratios in poor metabolizers. Safety evaluations, including electrocardiograms, indicated that the combination was well tolerated, with no difference between extensive and poor metabolizer phenotypes.
Postmortem proteolysis and calpain/calpastatin activity in callipyge and normal lamb biceps femoris during extended postmortem storage. (1999)

The present experiment was conducted to determine whether calpastatin inhibits only the rate, or both the rate and extent, of calpain-induced postmortem proteolysis. Biceps femoris from normal (n = 6) and callipyge (n = 6) lamb was stored for 56 d at 4 degrees C. Calpastatin activity was higher (P < .05) in the callipyge muscle at 0 and 14 d postmortem, but not at 56 d postmortem. The activity of mu-calpain did not differ between normal and callipyge biceps femoris at 0 and 56 d postmortem (P > .05), but was higher at 14 d postmortem in the callipyge muscle (P < 0.05). The activity of m-calpain was higher in the callipyge muscle (P < 0.05). Western blot analyses of titin, nebulin, dystrophin, myosin heavy chain, vinculin, alpha-actinin, desmin, and troponin-T indicated that postmortem proteolysis was less extensive in callipyge than in normal biceps femoris at all postmortem times. The results of this experiment indicate that calpastatin inhibits both the rate and extent of postmortem proteolysis.
Nonlinear dynamics of a gas bubble in an incompressible elastic medium (2004)

A nonlinear model in the form of the Rayleigh-Plesset equation is developed for a gas bubble in an essentially incompressible elastic medium such as a tissue or rubberlike medium. Two constitutive laws for the elastic medium are considered: the Mooney potential, and Landau's expansion of the strain energy density. These two constitutive laws are compared at quadratic order to obtain a relation between their respective elastic constants. Attention is devoted to the relative importance of shear stress on the bubble dynamics, allowing for the equilibrium gas pressure in the bubble to differ substantially from the pressure at infinity. The model for the bubble motion is approximated to quadratic order to assess the importance of shear stress in the surrounding medium relative to that of the gas pressure in the bubble. Relations are derived for the value of the shear wave speed at which the two contributions are comparable, which provide an assessment of when shear stress in the surrounding medium must be taken into account when modeling bubble dynamics.
Synchrotron serial crystallography with multi-stage merging of 1000's of images (2017)

and Blend [2] provide particularly effective tools to automatically manage the merging of large numbers of data sets from synchrotron serial crystallography. The requirement for manual intervention in the process can be reduced by extending Blend to support additional clustering options to improve the sensitivity to differences in unit cell parameters and to allow for clustering of nearly complete datasets on the basis of intensity differences. One applies KAMO twice, first using cell parameters. In this step either the simple cell vector distance of the original Blend is used, or the more sensitive NCDist [3], to find clusters to merge to at higher levels of completeness. In the second step one uses KAMO again using the correlation between the intensities at the common HKLs [4] to merge clusters in a way sensitive to structural differences that may not perturb the cell parameters sufficiently to make meaningful clusters.