gebhart/patrepeval huggingface dataset:
Neisseria species as pathobionts in bronchiectasis (2022)

Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.
Some families of Jensen-like inequalities with application to information theory (2023)

It is well known that the traditional Jensen inequality is proved by lower bounding the given convex function, $f(x)$, by the tangential affine function that passes through the point $(E\{X\},f(E\{X\}))$, where $E\{X\}$ is the expectation of the random variable $X$. While this tangential affine function yields the tightest lower bound among all lower bounds induced by affine functions that are tangential to $f$, it turns out that when the function $f$ is just part of a more complicated expression whose expectation is to be bounded, the tightest lower bound might belong to a tangential affine function that passes through a point different than $(E\{X\},f(E\{X\}))$. In this paper, we take advantage of this observation, by optimizing the point of tangency with regard to the specific given expression, in a variety of cases, and thereby derive several families of inequalities, henceforth referred to as ``Jensen-like'' inequalities, which are new to the best knowledge of the author. The degree of tightness and the potential usefulness of these inequalities is demonstrated in several application examples related to information theory.
Predicting Accurate Electronic Excitation Transfer Rates via Marcus Theory with Boys or Edmiston−Ruedenberg Localized Diabatization<sup>†</sup> (2010)

We model the triplet-triplet energy-transfer experiments from the Closs group [ Closs , G. L. ; et al. J. Am. Chem. Soc. 1988 , 110 , 2652. ] using a combination of Marcus theory and either Boys or Edmiston-Ruedenberg localized diabatization, and we show that relative and absolute rates of electronic excitation transfer may be computed successfully. For the case where both the donor and acceptor occupy equatorial positions on a rigid cyclohexane bridge, we find beta(calc) = 2.8 per C-C bond, compared with the experimental value beta(exp) = 2.6. This work highlights the power of using localized diabatization methods as a tool for modeling nonequilibrium processes.
Detection of Fecal Contamination on Cantaloupes Using Hyperspectral Fluorescence Imagery (2005)

ABSTRACT To determine whether detection of fecal contamination on cantaloupes is possible using fluorescence imaging, hyperspectral images of cantaloupes artificially contaminated with a range of diluted bovine feces were acquired from 425 to 774 nm in responses to ultraviolet‐A (320 to 400 nm) excitation. Evaluation of images at emission peak wavelengths indicated that 675 nm exhibited the greatest contrast between feces contaminated and untreated surface areas. Two‐band ratios compared with the single‐band images enhanced the contrast between the feces contaminated spots and untreated cantaloupe surfaces. The 595/655‐nm, 655/520‐nm, and 555/655‐nm ratio images provided relatively high detection rates ranging from 79% to 96% across all feces dilutions. However, both single band and ratio methods showed a number of false positives caused by such features as scarred tissues on cantaloupes. Principal component analysis (PCA) was performed using the entire hyperspectral images data; 2nd and 5th principal component (PC) image exhibited differential responses between feces spots and false positives. The combined use of the 2 PC images demonstrated the detection of feces spots (for example, minimum level of 16‐μg/mL dry fecal matter) with minimal false positives. Based on the PC weighing coefficients, the dominant wavelengths were 465, 487, 531, 607, 643, and 688 nm. This research demonstrated the potential of multispectral‐based fluorescence imaging for online applications for detection of fecal contamination on cantaloupes.
Dual‐wavelength hybrid optoacoustic‐ultrasound biomicroscopy for functional imaging of large‐scale cerebral vascular networks (2018)

A critical link exists between pathological changes of cerebral vasculature and diseases affecting brain function. Microscopic techniques have played an indispensable role in the study of neurovascular anatomy and functions. Yet, investigations are often hindered by suboptimal trade-offs between the spatiotemporal resolution, field-of-view (FOV) and type of contrast offered by the existing optical microscopy techniques. We present a hybrid dual-wavelength optoacoustic (OA) biomicroscope capable of rapid transcranial visualization of large-scale cerebral vascular networks. The system offers 3-dimensional views of the morphology and oxygenation status of the cerebral vasculature with single capillary resolution and a FOV exceeding 6 × 8 mm<sup>2</sup> , thus covering the entire cortical vasculature in mice. The large-scale OA imaging capacity is complemented by simultaneously acquired pulse-echo ultrasound (US) biomicroscopy scans of the mouse skull. The new approach holds great potential to provide better insights into cerebrovascular function and facilitate efficient studies into neurological and vascular abnormalities of the brain.
Spin-wave frequency discretization in submicron rectangular prisms (2003)

Spin-wave frequency discretization has been observed by Brillouin light scattering in an array of tangentially magnetized 800 nm×550 nm Ni81Fe19 rectangular prisms with thicknesses of 30 nm and dot separations of 200 nm. For a large wave vector interval, several discrete dispersionless modes were observed. The experimental frequencies were compared to those calculated using a recently developed analytical model for flat uniformly magnetized rectangular prisms. The agreement between the experimental and calculated frequencies is very good. In addition to the above mentioned modes, a low frequency mode was experimentally detected over a wide range of transferred wave vectors. Finally, the decrease in frequency of the first perpendicular standing spin-wave mode, observed in the patterned sample with respect to in the continuous film, was successfully reproduced.
Abstract P1-11-03: VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers (2023)

Abstract The brain is a common target organ for breast cancer metastasis, and the risk of brain metastasis is usually high for patients with HER2-positive breast cancer. While T-DXd showed positive results in HER2-positive breast cancer brain metastasis (BCBM), its activity and blood-brain barrier (BBB) permeability in active BCBM need to be further validated (TUXEDO-1 included 15 patients with active brain metastasis). Tucatinib plus Trastuzumab and Capecitabine triplet showed efficacy in patients with brain metastasis, but Tucatinib alone has poor BBB penetration. There is still an unmet medical need for active HER2-positive BCBM. VRN101099 is a highly selective kinase inhibitor of HER2 (Eurofins scanMAX Kinase Profiling, S-score (35) of 0.01). VRN101099 has single- to double-digit nanomolar (IC50) cellular potency in HER2-dependent cancer cells, and Ba/F3 cells expressing HER2 wild type or mutations with selectivity over wildtype EGFR. VRN101099 inhibited proliferation of BT474 with 3.6 nM IC50 but HaCaT with 829.2 nM IC50. VRN101099 binds HER2 kinase by forming a covalent bond to the Cys805 and its irreversible inhibition resulted in a longer target resident time than Tucatinib, confirmed by in vitro washout experiments. Robust in vivo activity of VRN101099 was observed in HER2-positive BT474 xenograft models. Moreover, once daily oral administration of VRN101099 significantly regressed intracranial BT474 tumor, demonstrating greater efficacy than twice daily oral administration of Tucatinib. These results were well explained by the superior brain to plasma exposure of VRN101099 to Tucatinib. Also, VRN101099 showed high exposure in the target organ, the fat pad, which potentiated better clinical translation. These anti-tumor efficacies are correlated with pharmacodynamic responses, as confirmed by decreased HER2, AKT, and ERK phosphorylation. In summary, VRN101099 is a brain penetrant, orally bioavailable, irreversible, and highly selective inhibitor of HER2 with therapeutic potential in HER2-positive BCBM. These data support the clinical development of VRN101099 in HER2-driven cancers. Citation Format: Yikyung Ko, Jihye yoo, Hong-ryul Jung, Hyerim Lim, YeongDeok Lee, Se Hyuk Kim, Dong Guk Shin, Serin Cho, Myung hoe Heo, Haelee Kim, Ha Yeon Cho, Ah Reum Han, Eunhwa Ko, Hwan Geun Choi, Deakwon Kim, Sunghwan Kim. VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-03.
An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence (2017)

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.
Program plan for the development, evaluation, and application of the Terrain-Responsive Atmospheric Code (TRAC) (1989)

The Department of Energy (DOE) maintains a number of atmospheric dispersion models at several facilities. DOE applies modeling for Risk Assessment, Emergency Response, and Regulatory Compliance. The Rocky Flats Plant is developing a dispersion/dose code to meet DOE and other governmental requirements for dispersion modeling at the Rocky Flats Plant. The Terrain-Responsive Atmospheric Code (TRAC) is designed to realistically simulate the involved atmospheric conditions that occur around complex sites such as the Rocky Flats. Our approach complements the fundamental research programs at DOE National Laboratories and other facilities. Proven research results are quickly transferred from the literature to applied use. In this way, the benefits of DOE-funded basic research are most rapidly realized. 16 refs., 22 figs., 13 tabs.
P5713Clinical pharmacology of AZD9977, a novel, selective mineralocorticoid receptor (MR) modulator without K+-sparing properties (2019)

Abstract Background and purpose Excessive MR activation is implicated in the pathogenesis of cardiovascular disease. MR antagonists (MRA) are effective and key guideline-directed therapy in patients with heart failure (HF) with reduced ejection fraction. However, clinical adverse events due to hyperkalaemia and a decline in renal function significantly restricts the treatment. AZD9977 is a novel, non-steroidal selective MR modulator that, compared with MRA, displays a differentiated MR-binding pattern and cofactor recruitment profile, and exerts similar organ protective effects to eplerenone with minimal effects on urinary electrolyte handling. Methods We performed a randomized, placebo-controlled, single-blind phase 1 study to evaluate the safety, tolerability and pharmacokinetics of oral AZD9977 in healthy men. Three sequential ascending dose cohorts were evaluated, and participants received either AZD9977 (n=6) or placebo (n=3) for 8 days. AZD9977 target doses of 50mg bid, 150mg bid and 300mg bid were explored based on a model predicted dose range comparable to and exceeding the target receptor occupancy levels achieved with approved MRA drugs. The dose of AZD9977 50mg bid is predicted to be equipotent to spironolactone 25mg daily. Results 27 healthy male subjects aged 23–45 years completed the study. All doses of AZD9977 were well tolerated with no safety concerns identified. A total of 7 adverse events occurred in 4 participants (22.2%) receiving AZD9977 and 8 events occurred in 6 participants (66.7%) receiving placebo, none severe or resulting in withdrawal from the study. Rapid absorption of AZD9977 was observed with median Tmax values ranging from 0.5 to 0.8-hours post-dose and approximate dose proportional kinetics between 50 to 300 mg twice daily, as measured by AUCτ and Cmax. Steady-state levels in plasma were generally reached within 3–4 days. Target engagement was confirmed by a robust dose-dependent rise in mean serum aldosterone levels between Day −1 and Day 7 (Placebo = 43±172pmol/L, AZD9977 50mg bid = 132±83pmol/L, 150mg bid = 447±242pmol/L, 300mg bid = 808±330pmol/L; Figure 1). AZD9977 had no effect on blood pressure or heart rate and did not alter serum electrolyte levels, urinary Na+ excretion, log urinary Na+/K+ ratio (Figure 2), estimated GFR, or urine volumes when compared to placebo-treated subjects. Figure 1 and Figure 2 Conclusion These observations in humans are consistent with pre-clinical studies, demonstrating robust MR-receptor engagement without changes in serum K+ and renal electrolyte handling. These characteristics could potentially realise the therapeutic benefit of MR blockade with a low risk of hyperkalaemia. This hypothesis is currently being tested clinically in a head-to-head trial of AZD9977 versus spironolactone in patients with HF and impaired renal function (NCT03682497). Acknowledgement/Funding The study was Sponsored and funded by AstraZeneca
Hepatic Clearance of ONO-5046, a Novel Neutrophil Elastase Inhibitor, in Rats and in the Rat Perfused Liver (1998)

The hepatic clearance of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy)phenylsulphonylamino]benz oyl]aminoacetic acid), a low-molecular-weight neutrophil elastase inhibitor, has been investigated in rats and in the rat perfused liver. This ester was easily hydrolysed to its inactive metabolite EI-601 (N-[2-[(4-hydroxyphenyl)sulphonylamino]benzoyl]aminoacetic acid) in liver homogenate and in erythrocytes suspension in-vitro. On the other hand, it was stable in biological media such as plasma and whole blood, which contain plasma proteins. Scatchard plot analysis of ONO-5046 binding to bovine serum albumin (BSA) in-vitro indicated that the association constant (K) and number of binding sites (n) were 6.91 x 10(4) (M(-1)) and 4.33, respectively. Thus, ONO-5046 (100 microM) would bind to plasma proteins to an extent >99% at physiological plasma-protein concentrations. The total plasma clearance of ONO-5046 in rats was constant (approximately 9 mL min(-1) kg(-1)) under different steady-state plasma concentrations (5-50 microM) a value equivalent to the hepatic clearance. In the rat perfused liver, the hepatic extraction ratio of ONO-5046 was significantly reduced by adding BSA to the dosing solution. Thus, the relatively low hepatic clearance of ONO-5046, which has an ester linkage in its structure and is naturally susceptible to enzymatic hydrolysis, was found to be because of the extremely high protein-binding of the compound.
Epigenetic Error and Large-scale Genomic Instability in Cancer (2018)

From an evolutionary point of view, it is likely that epigenetic markers arose as a means of protecting genetic information [1]. The primary epigenetic marker is DNA methylation and DNA methylation would furnish a way to distinguish between ‘self’ and ‘foreign’ genetic material as, for example, for the selective action of the restriction endonuclease system in bacteria [2].
The Concentrations of Retinol-Binding Protein, Prealbumin, and Transferrin in the Sera of Newly Delivered Mothers and Children of Various Ages (1975)

Umbilical-cord blood from 50 full-term newborns and capillary or venous blood from 226 children varying in age from 6 weeks to 16 years was examined for content of retinol-binding protein (RBP), prealbumin, and transferrin. The mean levels of the three proteins in the newborns were 21 mug/ml, 128 mug/ml, and 1.65 mg/ml, respectively. The corresponding maternal levels were 39 mug/ml, and 3.2 mg/ml. Paired serum values of mothers and newborns showed a correlation for both RBP and prealbumin but not for transferrin. The low levels of RBP at birth (about 50 per cent of that of nonpregnant women) increased rapidly over the first 6 months to a maximum of 31 mug/ml but declined thereafter to a mean level of about 26 mug/ml, which was maintained until the age of puberty when adult values were gradually attained. In serum, the prealbumin levels showed a similar development, whereas the transferrin values reached constant adult levels as early as 2 years of age.
Extracorporeal Photopheresis: Scientific and Technical Considerations for Improving Clinical Management of Patients (2014)

International audience
Effects of deep-level defects on ohmic contact and frequency performance of AlGaN/GaN high-electron-mobility transistors (2003)

We have characterized AlGaN/GaN high-electron-mobility-transistors on sapphire and silicon carbide substrates with electrical and microcathodoluminescence spectral measurements. Quarter wafer-scale comparisons of spectral features in the GaN attributed to donor–acceptor pair (DAP) transitions and yellow luminescence (YL) from deep acceptors show that the specific contact resistance is related to the ratio of the DAP to YL defect emission intensities. This suggests that these defects interact to change the contact resistance locally on the GaN side of the AlGaN/GaN interface. We show that changes in the frequency response of these transistors can be attributed to these defects at the interface.
Link Characterization and Edge-Centric Predictive Modeling in an Ocean Network (2023)

One of the critical problems fishermen face in deep-sea fishing is the lack of low-cost communication mechanisms to the shore. The Offshore Communication Network (OCN) is a network of fishing vessels at sea whose goal is to provide wireless internet over the ocean. The impact of extreme weather conditions on wireless signals, the inability to deploy additional infrastructure, the movements induced by sea waves, the expanded mobility freedom at sea, and the misalignment of directional antenna links are all unique challenges that cause abrupt signal quality fluctuations in OCN. For this reason, it is necessary to integrate near real-time link quality assessment to improve the resilience of communication. This paper examines the characteristics of marine wireless links and the factors impacting communication using data collected through sea-trial experiments involving multiple fishing vessels. The paper proposes a Bayesian framework for forecasting signal strength by employing historical and real-time data. This hybrid learning integrates offline and online probabilistic learning methods to provide intelligence at edge devices. The evaluation of the learning scheme on real datasets and the comparison with baseline methods under different communication contexts show improved predictive accuracy in OCN links.
A T-Cell Surface Molecule Different from CD2 is Involved in Spontaneous Rosette Formation with Erythrocytes (1988)

Increasing evidence indicates that rosettes which spontaneously from between human T cells and E might be of physiologic relevance. We show here that another T cell-surface molecule than CD2 is involved in rosette formation. Four mAb have been obtained reacting with human T cells that block rosettes with E from many species, including autologous cells. They react with a molecule, we termed E2, which is actively synthetized by T and monocytic cells. Immunoprecipitation revealed a major 32-kDa band. Immunoblots revealed a major 32-kDa band and a minor 20-kDa band. This molecule was detected on all T cells tested--and present at high densities on corticothymocytes, but at low densities on medullary thymocytes. It was also found on monocytes but not on B cells. However B-CLL cells did carry this molecule. E2 molecules were also detected on nonhematologic cells. Together with the recent evidence that 3 molecules from the erythrocyte surface are also involved for rosettes, intricate molecular interactions would account for adhesion of T cells to autologous E and possibly autologous nucleated cells.
Design and Synthesis of Chained-Response Multiband Filters (2019)

Given how important multiband filters are in the current era, little work seems to have come up with methods that can produce multiband filters of more than two passbands with flexibility in inner-band frequency selection, as well as specific bandwidths for each passband. In this paper, a novel method called the chained-response method is proposed. This method can produce multiband filters with the flexibility to specify accurately the bandwidths for each passband as well as its inner-band frequency selection. This paper describes the design procedure for this method. In order to validate the design procedure, a symmetrical dual-passband filter with bandwidths of 0.2 GHz for both passbands is designed. In order to show the novelty of this method, which is the flexibility of inner-band frequency selection and the specific bandwidths, an asymmetrical dual-passband filter with bandwidths of 0.2 GHz and 0.4 GHz is designed. Both the symmetrical and asymmetrical dual-passband filters are fabricated with a waveguide structure and the measurement results for both show good agreement with the theoretical ones. Finally, the mathematical modelling for a symmetric triple-passband filter and a symmetric quad-passband filter are briefly discussed to show how the proposed method can be expanded for designing filters with more than two passbands.