gebhart/patrepeval huggingface dataset:
Survey of X-ray induced Cherenkov excited fluorophores with potential for human use (2021)

X-ray induced molecular luminescence (XML) is a phenomenon that can be utilized for clinical, deep-tissue functional imaging of tailored molecular probes. In this study, a survey of common or clinically approved fluorophores was carried out for their megavoltage X-ray induced excitation and emission characteristics. We find that direct scintillation effects and Cherenkov generation are two possible ways to cause these molecules' excitation. To distinguish the contributions of each excitation mechanism, we exploited the dependency of Cherenkov radiation yield on X-ray energy. The probes were irradiated by constant dose of 6 MV and 18 MV X-ray radiation, and their relative emission intensities and spectra were quantified for each X-ray energy pair. From the ratios of XML, yield for 6 MV and 18 MV irradiation we found that the Cherenkov radiation dominated as an excitation mechanism, except for aluminum phthalocyanine, which exhibited substantial scintillation. The highest emission yields were detected from fluorescein, proflavin and aluminum phthalocyanine, in that order. XML yield was found to be affected by the emission quantum yield, overlap of the fluorescence excitation and Cherenkov emission spectra, scintillation yield. Considering all these factors and XML emission spectrum respective to tissue optical window, aluminum phthalocyanine offers the best XML yield for deep tissue use, while fluorescein and proflavine are most useful for subcutaneous or superficial use.
New-Onset Inflammatory Bowel Disease During Tumor Necrosis Factor-Alpha Inhibitor Therapy for Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis: A Review of the Food and Drug Administration Adverse Event Reporting System and Literature (2012)

Purpose: New-onset inflammatory bowel disease (IBD) has been reported as a paradoxical adverse event (PAE) in patients receiving tumor necrosis factor-alpha (TNF-α) inhibitors. We conducted a review of the Food and Drug Administration Adverse Event Reporting System (AERS) and published literature for cases of IBD reported in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) with TNF-α inhibitor therapy. Methods: The FDA AERS is a publicly available database of voluntary reports for post marketing surveillance of all approved drugs. 2,562,390 files from 2003 - June 2011 were downloaded and analyzed using SSPS 20 (IBM Co. Armonk, NY). Files were queried for reaction terms from the Dictionary for Regulatory Activities - inflammatory bowel disease, Crohn's disease (CD), ulcerative colitis (UC), and ulcerative proctitis reported with infliximab, etanercept, adalimumab, golimumab, and certolizumab and their trade names. “Primary suspect” reports were selected where indication for use was RA or JRA, (diseases are not associated with increased risk of IBD). A MEDLINE search was performed for published English language literature using MESH terms “inflammatory bowel disease/chemically induce”, “Crohn's disease/chemically induced”, and “ulcerative colitis/chemically induced” combined with the Boolean operator “OR” between terms. Additional articles were found in bibliographies of selected articles. Results: There were 183 cases of IBD after TNF-α inhibitor therapy (Table 1). The majority (95; 51.91%) were cases of CD, 61 (33.33%) were UC, and 27 (14.75%) were unspecified IBD. IBD was most commonly (105 cases; 57.37%) reported after etanercept and during therapy for RA. 77.4% of cases were females. The MEDLINE search revealed 30 previously described cases, 2 in RA patients (1 on infliximab and 1 on adalimumab) and 28 in JRA patients (26 on etanercept, 2 on infliximab). 26 JRA cases were histologically verified; 18 cases were CD, 3 were UC, and 5 were indeterminate IBD.Table 1: Inflammatory bowel disease with TNF-α inhibitor therapy reported to FDA AERSConclusion: TNF-α inhibitor therapy may be associated with new-onset of IBD and appears to occur most commonly in RA patients.
New Fused Cast Refractories for Glass Furnace Regenerators (2008)

In this paper, SEPR's technical investigation of the working conditions of industrial regenerators will be presented. The R&D approach of close-to-application test procedures used in new product development will be discussed followed by a very short overview of laboratory-scale test devices. Some of the results of SEPR's tests and studies will be presented. These results include the improvement of an AZS checker material for borosilicate glasses and a new fused cast AZS material for soda-lime glass regenerators operating under mild conditions. Finally, conclusions to date from this approach will be summarized.
Adsorption of plasmid DNA onto lipid/polymer particle assemblies (2009)

In this study, the adsorption of plasmid DNA onto preformed lipid/polymer particle assemblies was investigated. These assemblies, called LipoParticles, with a great potential in the biomedical field, were previously studied and thoroughly characterized. They consist of submicrometer anionic spherical polymer particles composed of either poly(styrene) or poly(lactic acid) which are coated with lipid layers formed by mixtures of zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cationic 1,2-dipalmitoyl-3-trimethylammonium-propane (DPTAP) in tunable proportions. The plasmid adsorption onto the LipoParticle surface was clearly established by the inversion of the surface charge of the assemblies, fluorescence microscopy observations, and agarose gel electrophoresis. From a quantitative standpoint, adsorption isotherms were found to be independent on the polymer core nature but rather strongly dependent on the adsorbed lipid shell composition. Furthermore, the data were fitted with the Langmuir model providing interesting information about the plasmid adsorption process such as the affinity constants between species, as well as the saturation levels of adsorbed plasmids onto assemblies. Finally, the compaction state of the adsorbed DNA was examined thanks to displacement experiments of a DNA-intercalated fluorescent dye, and found to be tightly related to the proportion of the cationic lipid in the adsorbed lipid layer. DPTAP-rich lipid formulations indeed displayed an important plasmid compaction that could be linked to a high affinity constant and a high amount adsorbed.
<title>Ring resonators for microwave optoelectronics</title> (1991)

Distributed transmission line theory is used to accurately model circular microstrip resonant structures. The model incorporates the effects of microstrip dispersion, conductor and dielectric loss, curvature, and the coupling capacitance of the feed lines. It is applied to study electronically tuned resonators and excellent agreement is obtained between theory and experiment. Microwave optoelectronic mixing is obtained by heterodyning a microwave local oscillator with a modulated optical carrier in a microstrip ring resonator on semi-insulating GaAs substrate.
Integrated Silicon-on-Insulator Spectrometer With Single Pixel Readout for Mid-Infrared Spectroscopy (2018)

Mid-infrared spectroscopy in the 2-4 μm wavelength range is of cardinal value for many sensing applications. Current solutions involve bulky and expensive systems to operate. Silicon-on-Insulator (SOI) waveguide technology offers means to miniaturize the different parts of the spectrometer. However, the development of on-chip detectors for the mid-infrared wavelength range is in its infancy and the characteristics are not on par with their discrete (cooled) counterparts. In this work, a compact and cheap mid-infrared spectrometer is realized by integrating a SOI arrayed waveguide grating (AWG) spectrometer operating in the 2.3 μm wavelength range with a high performance mid-infrared photodiode. The AWG has 12 output channels with a spacing of 225 GHz (4 nm) and a free spectral range of 3150 GHz (56 nm), which are simultaneously collected by a single, transistor outline (TO)-packaged extended InGaAs PIN photodiode. The response of each AWG channel is discerned by time-sequentially modulating the optical power in each output channel using integrated MachZehnder based thermo-optic modulators with a π-phase shift power consumption of ≈50 mW. As an example, the absorption spectrum of a 0.5 mm thick polydimethylsiloxane sheet is sampled and compared to a benchtop spectrometer to good agreement.
Clinical, Pathologic, and Functional Outcomes After Nephron-Sparing Surgery in Patients with a Solitary Kidney: A Multicenter Experience (2012)

Extirpation and ablation are both reasonable options for treatment. Ablation is more minimally invasive, albeit with higher recurrence rates compared with PN. Postoperative renal function is similar in both groups and is not affected by surgical approach.
CYP46A1 Activation By Low-Dose Efavirenz Enhances Brain Cholesterol Metabolism In Subjects With Mild Cognitive Impairment Due To Alzheimer’s Disease (2022)

Abstract Background: Efavirenz is an anti-HIV drug, and cytochrome P450 46A1 (CYP46A1) is a CNS-specific enzyme that metabolizes cholesterol to 24-hydroxycholesterol (24HC). We have previously shown that allosteric CYP46A1 activation by low-dose efavirenz in a transgenic mouse model of Alzheimer’s disease (AD) enhanced both cholesterol elimination and turnover in the brain and improved animal performance in memory tests. Here, we sought to determine whether CYP46A1 could be similarly activated by a low-dose efavirenz in human subjects. Methods: This pilot study enrolled 5 subjects with mild cognitive impairment due to AD. Participants were randomized to placebo (n=1) or two daily efavirenz doses (50 mg and 200 mg, n=2 for each) for 20 weeks and evaluated for safety and CYP46A1 target engagement (plasma 24HC levels). A longitudinal mixed model was used to ascertain statistical significance of target engagement . We also measured 24HC in CSF and conducted a unique stable isotope labeling kinetics (SILK) study with deuterated water to directly measure CYP46A1 activity changes in the brain. Results: In all subjects receiving efavirenz, there was a statistically significant increase ( P £ 0.001) in the levels of plasma 24HC. The levels of 24HC in the CSF of subjects on the 200 mg-dose of efavirenz were also increased. Target engagement was further supported by the labeling kinetics of 24HC by deuterated water in the SILK study. There were no serious adverse effects in any subjects. Conclusions: Our findings provide evidence of efavirenz target engagement in human subjects with AD. This supports pursuit of a larger trial for further determination and confirmation of the efavirenz dose that exerts maximal enzyme activation, as well as evaluation of this drug effects on AD biomarkers and clinical symptomatology. Trial registration: ClinicalTrials.gov NCT03706885.
Estimating a Separably Markov Random Field from Binary Observations (2018)

A fundamental problem in neuroscience is to characterize the dynamics of spiking from the neurons in a circuit that is involved in learning about a stimulus or a contingency. A key limitation of current methods to analyze neural spiking data is the need to collapse neural activity over time or trials, which may cause the loss of information pertinent to understanding the function of a neuron or circuit. We introduce a new method that can determine not only the trial-to-trial dynamics that accompany the learning of a contingency by a neuron, but also the latency of this learning with respect to the onset of a conditioned stimulus. The backbone of the method is a separable two-dimensional (2D) random field (RF) model of neural spike rasters, in which the joint conditional intensity function of a neuron over time and trials depends on two latent Markovian state sequences that evolve separately but in parallel. Classical tools to estimate state-space models cannot be applied readily to our 2D separable RF model. We develop efficient statistical and computational tools to estimate the parameters of the separable 2D RF model. We apply these to data collected from neurons in the prefrontal cortex in an experiment designed to characterize the neural underpinnings of the associative learning of fear in mice. Overall, the separable 2D RF model provides a detailed, interpretable characterization of the dynamics of neural spiking that accompany the learning of a contingency.
Targeting JAK-STAT Pathway for Various Inflammatory Diseases and Viral Infections (2020)

The Janus activating kinase (JAK)–signal transducer and activator of transcription (STAT) pathway has been implicated in many inflammatory diseases including autoimmune inflammatory disorders, malignancies such as myelofibrosis, and immune dysregulation pathologies. These diseases are hallmarked by either systemic- or tissue-localized hyperinflammatory responses including chronic elevation of key soluble inflammatory cytokines, such as IL-6, D-dimer, C Reactive Protein (CRP), TNF-α, IL-α/β, GM-CSF, and IFN-α/β. Recently, additional reports have highlighted the role of the JAK-STAT pathway in virus-induced inflammation, including HIV infection. Further, the JAK-STAT pathway is activated by engagement of CD4, a primary HIV receptor by HIV envelope gp120, resulting in autocrine and paracrine signaling of key inflammatory factors that promote HIV persistence, both systemically and across localized “hot spots” of inflammation including within the CNS. This review focuses on the role of the JAK-STAT pathway in various diseases, the implications of targeted, selective inhibition of JAKs by small molecule inhibitors, and the benefits of these agents versus widely used, non-specific anti-inflammatory or immunosuppressive agents.
Correction: ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection (2013)

[This corrects the article DOI: 10.1371/journal.ppat.1003632.].
Replication Protein A Is Required for Meiotic Recombination in Saccharomyces cerevisiae (2002)

In Saccharomyces cerevisiae, meiotic recombination is initiated by transient DNA double-stranded breaks (DSBs). These DSBs undergo a 5' --> 3' resection to produce 3' single-stranded DNA ends that serve to channel DSBs into the RAD52 recombinational repair pathway. In vitro studies strongly suggest that several proteins of this pathway--Rad51, Rad52, Rad54, Rad55, Rad57, and replication protein A (RPA)--play a role in the strand exchange reaction. Here, we report a study of the meiotic phenotypes conferred by two missense mutations affecting the largest subunit of RPA, which are localized in the protein interaction domain (rfa1-t11) and in the DNA-binding domain (rfa1-t48). We find that both mutant diploids exhibit reduced sporulation efficiency, very poor spore viability, and a 10- to 100-fold decrease in meiotic recombination. Physical analyses indicate that both mutants form normal levels of meiosis-specific DSBs and that the broken ends are processed into 3'-OH single-stranded tails, indicating that the RPA complex present in these rfa1 mutants is functional in the initial steps of meiotic recombination. However, the 5' ends of the broken fragments undergo extensive resection, similar to what is observed in rad51, rad52, rad55, and rad57 mutants, indicating that these RPA mutants are defective in the repair of the Spo11-dependent DSBs that initiate homologous recombination during meiosis.
Thermoelastic and Optical Properties of Thick Boride Templates on Silicon for Nitride Integration Applications (2008)

We present a comparative study of the structural, thermoelastic, and optical properties of ZrB2 films grown on silicon with the corresponding bulk ZrB2 behavior. Thick ZrB2 films (up to 500 nm) with device quality morphological and structural properties were grown on Si(111) for potential integration of GaN with Si substrates. HR-XRD was used to analyze the thickness and temperature dependence of the films’ strain state. The data indicate that at room temperature a residual tensile strain of ∼0.5% persists in all samples independent of thickness. When the films are heated back to the growth temperature of 900 °C, two distinct behaviors are observed: thinner films (∼200 nm) follow the thermal expansion of the Si substrate, which results in a tensile strain at the growth temperature. Thicker films (∼400 nm) are fully relaxed at 900 °C and thus decoupled from the substrate. These strain behaviors imply that hybrid ZrB2/Si(111) templates are better matched to GaN than any other known substrate. Comparison of the mismatch strains between sapphire, SiC, and bulk ZrB2 substrates with GaN films over a broad temperature range (20–900 °C) illustrates the superior structural and thermal characteristics of hybrid ZrB2/Si(111) templates for nitride integration. Measurements of the ZrB2 dielectric function ϵ(ω) and its reflectivity R(ω) were conducted in the 0.2–7 eV range on thin films and compared for the first time with density functional theory simulations. The dielectric function displays a typical metallic Drude behavior across the wide IR range, with a reflectivity approaching unity at the operational wavelengths of GaN-based intersubband devices. The characteristic Drude plasma energy and lifetimes are compared with those obtained from transport measurements in the isostructural MgB2 analogue. A detailed electronic structure analysis is also used to identify the interband transitions responsible for characteristic features observed at 2.5, 4.3, and 5.7 eV in the spectrum. Collectively our studies pave the way for understanding key optical and thermoelastic design parameters in novel conductive and reflective buffer layers for improved performance in nitride LEDs, fully integrated with silicon.
- Molecular biology of cystic fibrosis: CFTR processing and functions and classes of mutations (2015)

Cystic brosis (CF) is an autosomal recessive lethal disease caused by mutations in the cystic brosis transmembrane conductance regulator (CFTR) (ABCC7) gene located on the seventh chromosome. It aects 1 in 2500-4500 newborns among Caucasians. e clinical entity was recognized for the rst time in 1938 as a CF of the pancreas by Dorothy Hansine Andersen.1 e rst linkage between CF and a genetic marker, indicating that only one locus existed for CF, was established in 1985.2 e CFTR gene and its main mutation F508del were identied in 1989 by Francis Collins, Lap-Chee Tsui, and John R. Riordan.3 Subsequent research has found over 1900 dierent mutations, but less than 150 are actually known to cause CF. Current therapies treat the symptoms of the disease. However, a better understanding of the mechanisms of CFTR mutations now points to novel, mutation-targeted strategies correcting the underlying basic defects responsible for CFTR protein loss of function. is is because recent ndings have helped to decipher the complex biogenesis and function of the wild-type protein.
Identification of mRNA in the Slime MoldPhysarum polycephalum (1979)

Using a differential extraction procedure which had previously been shown to yield one nucleic acid fraction enriched in cytoplasmic RNA and another enriched in nuclear RNA, we have been able to isolate two polyadenylated RNA populations from microplasmodia of Physarum polycephalum. The poly(A)-containing RNA from the cytoplasmic-enriched fraction accounts for approximately 1.2% of the cytoplasmic nucleic acid, has a number-average nucleotide size of 1339 ± 39 nucleotides, and has been shown, in a protein-synthesizing system in vitro, to be capable of directing the synthesis of peptides which have also been shown to be synthesized in vivo by microplasmodia. The poly(A)-containing RNA from the nuclear-enriched fraction has a number-average nucleotide size of 1533 ± 104 nucleotides and represents a mixture of cytoplasmic and nuclear adenylated RNA molecules. Based upon these observations, we have identified the polyadenylated RNA isolated from the fraction enriched in cytoplasmic nucleic acid as Physarum poly(A)-containing messenger RNA.
Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis (2016)

Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.
Anterior insular cortex is necessary for empathetic pain perception (2012)

Empathy refers to the ability to perceive and share another person's affective state. Much neuroimaging evidence suggests that observing others' suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are 'necessary' for empathetic pain remains unknown. Herein, we examined the perception of others' pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others' pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning.