gebhart/patrepeval huggingface dataset:
Evaluation and Synthesis of Polar Aryl- and Heteroaryl Spiroazetidine-Piperidine Acetamides as Ghrelin Inverse Agonists (2014)

Several polar heteroaromatic acetic acids and their piperidine amides were synthesized and evaluated as ghrelin or type 1a growth hormone secretagogue receptor (GHS-R1a) inverse agonists. Efforts to improve pharmacokinetic and safety profile was achieved by modulating physicochemical properties and, more specifically, emphasizing increased polarity of our chemical series. ortho-Carboxamide containing compounds provided optimal physicochemical, pharmacologic, and safety profile. pH-dependent chemical stability was also assessed with our series.
Impact of Hard Machining on Zirconia Based Ceramics for Dental Applications (2017)

Since the late 90s the use of zirconia based all-ceramic restorations increases. Many manufacturing steps are necessary, like pre-sintering, soft machining (pre-sintered condition), sintering and hard machining (fully sintered) in combination with a final staining or veneering step. All these techniques, especially hard machining, are associated with the production of flaws in different scales, in conjunction with thermal and residual stresses and phase transformations. These are inter alia capable to induce failure. This work investigates the impact of hard machining on the material properties and attempts to establish a correlation to failure.
Thermal transients in a U-bend (2019)

We study numerically the propagation of a hot thermal transient through a U-bend via an ensemble of wall-resolved large eddy simulations. Conjugate heat transfer between fluid and solid domains is accounted for. The flow is in a fully turbulent mixed convection regime, with a bulk Reynolds number of 10,000, a Richardson number of 2.23, and water as the working fluid (Prandtl number = 6). These conditions lead to strong thermal stratification, with buoyancy-induced secondary flows, and the generation of a large and persistent recirculation region. The evolution of Dean vortices as the thermal transient passes is studied. It is found that baroclinic vorticity generation dominates over a large period of the transient, due to the thermal inertia of the wall. Gravitational buoyancy leads to a reversal of the counter-rotating vortex pair. The impact of this reversal on the swirl-switching and secondary-current losses is assessed. It is found that low frequency modes are suppressed in the reversed-vortex state.
Tumor Targeting and Imaging Using Cyclic RGD‐PEGylated Gold Nanoparticle Probes with Directly Conjugated Iodine‐125 (2011)

Radioactive iodine-labeled, cyclic RGD-PEGylated gold nanoparticle (AuNP) probes are designed and synthesized for targeting cancer cells and imaging tumor sites. These iodine-125-labeled cRGD-PEG-AuNP probes are stable in various conditions including a range of pHs and high salt and temperature conditions. These probes can target selectively and be taken up by tumor cells via integrin αvβ3-receptor-mediated endocytosis with no cytotoxicity. The probes show a significant increase in the avidity of αvβ3 integrin compared to the corresponding free cRGD peptides. In-vivo SPECT/CT imaging results show that the iodine-125-labeled cRGD-PEG-AuNP probes can target the tumor site as soon as 10 min after injection, and also that cyclic RGD peptides are needed for efficient and long-term in-vivo monitoring. The results suggest that the probes circulate through the whole body, including renal filtration, and are excretable. These promising results show that radioactive-iodine-labeled gold nanoprobes have potential for highly specific and sensitive tumor imaging or for use as angiogenesis-targeted SPECT/CT imaging probes.
Comprehensive and temporal analysis of secreted proteins in the medium from IL‐6 exposed human hepatocyte (2014)

We have previously identified intracellular secretory acute phase response (sAPR) proteins in human hepatocytes following interleukin-6 (IL-6) induction by fluorogenic derivatization (FD)-liquid chromatography (LC)-tandem mass spectrometry (MS/MS). In this report, we utilized this method, which uses 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-Cl) as the FD reagent, to comprehensively and time-dependently analyze secreted proteins in the medium, including sAPR proteins. Since DAABD-Cl selectively reacts with thiol moieties of cysteinyl residues, direct derivatization, high-resolution LC separation and identification of the secreted proteins in the culture medium were successfully achieved without a pretreatment step. As a result, 14 sAPR proteins were identified simultaneously during a 72 h induction by IL-6. The secretion levels of 11 proteins increased, whereas the secretion levels of three important transport proteins decreased (albumin, retinol-binding protein 4 and transthyretin). In addition, the secretion level of a haptoglobin was found to increase significantly between 0 and 6 h by 1.88-fold compared with the control sample. The secretion levels of four cytoplasmic proteins increased: LDH, a known marker for cell damage, and GSTA1, FABP1 and ADH1B, which are marker proteins for hepatocellular damage. The secretion levels of the other two newly identified cytoplasmic proteins, profilin-1 and SOD2, were also found to increase, suggesting that these two proteins represent novel markers for cell damage. These results suggest that the FD-LC-MS/MS proteomics method can be used to analyze comprehensively and time-dependently the secreted proteins and thereby can offer information that aids our understanding of the dynamics of protein secretion affected by the exposure of cytokines such as IL-6.
Two-particle decays of theBCmeson into charmonium states (2002)

The factorization of hard and soft contributions into the hadronic decays of B_c meson at large recoils is explored in order to evaluate the decay rates into the S, P and D-wave charmonia associated with rho and pi. The constraints of approach applicability and uncertainties of numerical estimates are discussed. The mode with the J/psi in the final state is evaluated taking into account the cascade radiative electromagnetic decays of excited P-wave states, that enlarges the branching ratio by 20-25%.
[Alprostadil Reference Standard (Control 001) of National Institute of Health Sciences]. (2001)

The raw material of Alprostadil was examined for the preparation of "Alprostadil Reference Standard (Control 001)". Analytical data obtained were: IR spectrum, same as that of the Alprostadil Reference Standard (Control 923); thin-layer chromatography, no impurities were detected until 20 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.2%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Alprostadil Reference Standard (Control 001).
Procedure for Measuring and Reporting the Performance of Photovoltaic Systems in Buildings (2005)

This procedure provides a standard method for measuring and characterizing the long-term energy performance of photovoltaic (PV) systems in buildings and the resulting implications to the building's energy use. The performance metrics determined here may be compared against benchmarks for evaluating system performance and verifying that performance targets have been achieved. Uses may include comparison of performance with the design intent; comparison with other PV systems in buildings; economic analysis of PV systems in buildings; and the establishment of long-term performance records that enable maintenance staff to monitor trends in energy performance.
The hazard of exposure to impulse noise as a function of frequency. (1992)

Existing criteria for safe exposure to impulse noise do not consider the frequency spectrum of an impulse as a variable in the evaluation of the hazards to the auditory system. This report presents the results of a study that was designed to determine the relative potential that impulsive energy concentrated at different frequencies has in causing auditory system trauma. One hundred and thirty (130) chinchilla, divided into 22 groups with 5 to 7 animals per group, were used in these experiments. Pre- and post-exposure audiograms were measured on each animal using avoidance conditioning procedures. Quantitative histology (cochleograms) was used to determine the extent and pattern of the sensory cell damage. The noise exposure stimuli consisted of seven different computer-generated narrow-band impulses (approximately 400-Hz bandwidth) having center frequencies located at 0.260, 0.775, 1.025, 1.350, 2.075, 2.450, and 3.550 kHz. Each narrow-band exposure stimulus was presented at two to four different intensities. An analysis of the audiometric and histological data allowed an iso-hazard weighting function to be derived. The weighting function clearly demonstrates that equivalent amounts of impulsive energy concentrated at different frequencies are not equally hazardous to the auditory system. Comparison of the derived weighting function with the A-weighting curve indicates low frequency impulses are less hazardous than predicted by A-weighted sound exposure level.
The free educational prison: metaphors and images (1996)

Summary The purpose of the present study, based on thousands of metaphorical images gathered from hundreds of students and educators, is to enlighten empirically some basic perceptions that may enhance our understanding of the problems and difficulties which face schooling. The wide range of metaphorical images can be a fruitful springboard for teacher training and changing educational practice. The analysis is organized in four sections: the pupil, the teacher, the principal and the school, underscoring what seems to be one of the major contradictions in schooling: the free educational prison. The study is a simultaneous view of the open educational character of schooling and its imprisoning effect. The finding of a significant discrepancy between students’ perceptions of themselves, the educators and the school, and of the educators’ perception of students poses a challenge to the schooling system.
Multi-field Correlated Topic Modeling (2009)

Popular methods for probabilistic topic modeling like the Latent Dirichlet Allocation (LDA, [1]) and Correlated Topic Models (CTM, [2]) share an important property, i.e., using a common set of topics to model all the data. This property can be too restrictive for modeling complex data entries where multiple fields of heterogeneous data jointly provide rich information about each object or event. We propose a new extension of the CTM method to enable modeling with multi-field topics in a global graphical structure, and a mean-field variational algorithm to allow joint learning of multinomial topic models from discrete data and Gaussian-style topic models for real-valued data. We conducted experiments with both simulated and real data, and observed that the multi-field CTM outperforms a conventional CTM in both likelihood maximization and perplexity reduction. A deeper analysis on the simulated data reveals that the superior performance is the result of successful discovery of the mapping among field-specific topics and observed data.
p53 Inhibitors as Cancer Sensitizing Agents (2008)

The formation and the development of neoplasia is a Darwinian selection for cells that progressively lose negative regulators and simultaneously reinforce positive modulators of growth. For example, the regulatory mechanisms involved in checkpoint control and apoptosis are needed to guarantee genetic stability for healthy cells, but are detrimental for cancer cells. The possibility to pharmacologically tune such regulatory systems in cancer therapy represents a big challenge to selectively destroy cancer cells and protect healthy cells, thus favoring regeneration and tissue recovery. One well-known key player of such regulatory mechanisms is p53. p53 is activated following different stresses, including altered signals from the environment, DNA damage by chemical and physical agents (genotoxic stress), altered assembly/disassembly of microtubules, oncogene activation and hypoxia [1-3]. All these cellular stresses result in cell-cycle arrest, apoptosis and/or DNA repair, depending on the cell type, their developmental time point, the character and the entity of the insult (Fig. 12.1) [4, 5]. However, the proper cellular stress-response is also orchestrated by p53 through the choice of its partners and its transcriptional readout [6–8]. Following cellular insults, there are three major decision points. The first one occurs after DNA damage and directs cells toward apoptosis or DNA repair. The second one occurs after DNA repair and establishes whether or not repair was successful and whether cells can resume proliferation. The third one happens when repair was unsuccessful. In this case cells must choose between irreversible growth arrest and mitotic catastrophe. In all three decision points, p53 is one major actor, and which function p53 ensures is also determined by the amount and duration of p53 activation. Indeed, strong and sustained p53 activation correlates with higher chances for apoptosis versus growth arrest [9]. The success of and the requirement for DNA damage repair after genotoxic stresses both largely depend on the proliferation rate of cells. For example, unrepaired chromosomal breaks can be lethal for dividing cells, but tolerated by quiescent cells that will never detect such damage being postmitotic. One of the best examples is the radiosensitivity of the brain, which is one of the most radioresistant organs in the adult, but the most sensitive one in embryos [10]. Thus, p53 has an important “social” function: ensuring DNA repair or elimination of irreversibly damaged and, consequently, dangerous cells, by inducing them to die for the benefit of the organism. All these functions unambiguously state the role of p53 as a key tumor suppressor gene. Mutation of the p53 gene is found in more than 50% of human Chapter 12 p53 Inhibitors as Cancer Sensitizing Agents
White's Classification of Diabetes in Pregnancy in the 21st Century: Is It Still Valid? (2009)

White's classification system (WCS) was created 60 years ago to identify diabetic (DM) pregnancies at increased risk for perinatal morbidity and mortality. Our objective was to assess the association between WCS and adverse pregnancy outcome (APO) in contemporary DM pregnancies. We studied diabetic women with singleton pregnancies who delivered at >20 weeks at a single institution over a 1-year period (2007 to 2008). Perinatal outcomes were compared between WCS groups. APO was defined as any of the following: preterm birth <34 weeks, severe preeclampsia, shoulder dystocia, and neonatal respiratory disease. Presence of vascular disease was defined as presence of chronic hypertension, chronic renal insufficiency, retinopathy, coronary artery disease, or prior cerebrovascular event. One hundred ninety-six DM pregnancies met the criteria. No significant differences in APO existed between White's class groups among women with pregestational DM (32.7% class B versus 26.9% class C versus 57.1% class D to F; p = 0.46). Logistic regression revealed that vascular disease was associated with APO (odds ratio = 2.7, 95% confidence interval = 1.2 to 6.2). In our population, presence of vascular disease, rather than WCS, was a better predictor of APO in DM women.
Modulation of actomyosin ATPase by thin filament-associated proteins. (1987)

Phosphorylation of the myosin light chain is a prerequisite for actin-activation of the Mg-ATPase of smooth muscle myosin. However, maximal activation of the Mg-ATPase by actin requires stoichiometric binding of tropomyosin to actin filaments and Ca2+ at free Mg2+ below 3 mM. The requirement for Ca2+ for actin-activation is not due to a calcium-mediated binding of tropomyosin to actin since the binding of tropomyosin to actin is not dependent on Ca2+. Caldesmon, an actin and calmodulin binding protein, at caldesmon:actin molar ratio of 1:18, binds equally to pure actin and actin containing stoichiometric amounts of bound tropomyosin. The Mg-ATPase of myosin reconstituted with actin is not affected by the caldesmon; on the other hand, the activity of actomyosin containing tropomyosin is inhibited. The inhibition of activity by the caldesmon is reversed by the addition of calmodulin (caldesmon:calmodulin molar ratio, 1:8) in the presence of Ca2+. The amount of caldesmon bound to actin in the presence of calcium-calmodulin is 50% more when actin filaments contain tropomyosin, indicating that the release of inhibition of the activity inhibited by caldesmon does not require complete release of caldesmon from actin.
Life history consequences of social complexity a comparative study of ground-dwelling sciurids (1998)

We examined life-history consequences of increased social complexity in ground-dwelling schnid rodents. We derived a continuous metric of social complexity from demographic data. Social complexity increased with the number of age-sex “roles” that interacted in a social group. Data were analyzed by computing phylogeneticaDy independent contrasts and by using phylogenetic autocorrelation to estimate and then remove the marimiim amount of variation in life-history variables that could be attributed to phylogenetic similarity. Analyses that incorporated estimates of phytogeny generated consistent results. As social complexity increased, a smaller proportion of adult females bred, there was a greater time to first reproduction, litter size decreased, and there was greater first-year offspring survival. Social complexity influenced neither gestation nor lactation time. Thus, social complexity has costs in terms of a reduction in the annual per-capita number of offspring produced but benefits in terms of enhanced offspring survival.
Quantitative Longitudinal Antibody Monitoring in a COVID-19 Outpatient Case Series: Relations of IgM/IgG Dynamics to Anosmia and Ageusia (2021)

A case series of 22 patients with confirmed SARS-CoV-2 infection and Corona Virus Disease 2019 (COVID-19) symptoms was followed in a primary care clinic. We provided quantitative and longitudinal profiling for SARS-CoV-2 IgM and IgG with a point of care device. Half the patients had a history of anosmia or ageusia. IgM and IgG responses were highly heterogeneous quantitatively and temporally. We determined that clinical symptomatology of chemosensory loss correlated with lesser but sustained titers of IgM and IgG whereas normal chemosensation correlated with transiently higher but rapidly declining antibody levels.
Glucose supplementation has minimal effects on blood neutrophil function and gene expression in vitro (2015)

During early lactation, glucose availability is low and the effect of glucose supply on bovine polymorphonuclear leukocyte (PMNL) function is poorly understood. The objective of this study was to determine the effect of glucose supplementation on the function and transcriptomic inflammatory response of PMNL from cows in early and mid-lactation in vitro. Twenty Holstein cows in early (n=10; days in milk=17±3.1) and mid-lactation (n=10; days in milk=168±14.8) were used for this study. Jugular blood was analyzed for serum concentrations of nonesterified fatty acids, β-hydroxybutyrate, and glucose. Polymorphonuclear leukocytes were isolated and diluted using RPMI (basal glucose concentration was 7.2 mM) to different concentrations of PMNL/mL for phagocytosis, chemotaxis, gene expression, and medium analyses. Working solutions of glucose (0 or 4 mM of d-glucose) and lipopolysaccharide (0 or 50μg/mL) were added and tubes were incubated for 120 min at 37°C. Media were analyzed for concentrations of glucose and tumor necrosis factor-α (TNF-α). Data were analyzed in a randomized block (stage of lactation) design. Challenge with lipopolysaccharide increased the expression of the genes encoding for nuclear factor kappa B (NFKB1), IL-10 (IL10), IL1B, IL6, IL8, TNF-α (TNFA), glucose transporter 3 (SLC2A3), and the concentration of TNF-α in medium (147.3 vs. 72.5 pg/mL for lipopolysaccharide and control, respectively). Main effect of stage of lactation was minimal where the expression of IL10 increased for cows in early compared with cows in mid-lactation. After lipopolysaccharide challenge, cows in early lactation experienced more marked increases in the expression of IL6, TNFA, and IL8 when compared with cows in mid-lactation. Glucose supplementation had minimal effects on gene expression where glucose supplementation increased the expression of lysozyme (LYZ). Glucose supplementation increased PMNL phagocytosis but did not alter chemotaxis, morphology, or concentration of TNF-α in the medium. Under the conditions of the experiment, stage of lactation had minimal effects on PMNL response to glucose supply where only the expression of NFKB1 and the production of TNF-α were greater for cows in mid-lactation when compared with early lactation. Metabolic profiles for cows in early lactation did not parallel those for cows during the early postpartum period and may partly explain results for this study. Future studies investigating the effect of glucose supply on bovine PMNL function in vivo and how this may be altered by stage of lactation are warranted.
Neuronal NOX4 knockdown alleviates pathological tau-related alterations in a humanized mouse model of tauopathy (2020)

Abstract Approximately 44 million people worldwide live with Alzheimer’s disease (AD) or a related form of dementia. Aggregates of the microtubule-associated protein tau are a common marker of these neurodegenerative diseases collectively termed as tauopathies. However, all therapeutic attempts based on tau have failed, suggesting that tau may only indicate a higher-level causal mechanism. For example, increasing levels of reactive oxygen species (ROS) may trigger protein aggregation or modulate protein degradation. Here we show that type 4 NADPH oxidase (NOX), the most abundant isoform of the only dedicated reactive oxygen producing enzyme family, is upregulated in dementia and AD patients and in a humanized mouse model of tauopathy. Both global knockout and neuronal knockdown of the Nox4 gene in mice, diminished the accumulation of pathological tau and positively modified established tauopathy by a mechanism that implicates modulation of the autophagy-lysosomal pathway (ALP). Moreover, neuronal-targeted NOX4 knockdown was sufficient to reduce neurotoxicity and prevented cognitive decline, suggesting a direct and causal role for neuronal NOX4. Thus, NOX4 is a previously unrecognized causal, mechanism-based target in tauopathies and blood-brain barrier permeable specific NOX4 inhibitors could have therapeutic potential even in established disease. Graphical abstract