gebhart/patrepeval huggingface dataset:
Diabetes Retinopathy (DR) Relates to Complication Risk in Young Persons with T1D (2018)

Young persons who develop DR may represent a high-risk group for early development of other complications. In young persons with youth-onset T1D, we evaluated associations between DR status and markers of other T1D complication risk. Youth (N=127), mean age 21.7 y (range 10.7-31.9), mean T1D onset 6.3 y (range 0.5-17.6) underwent DR assessment (ETDRS-protocol 7 field fundus photos); renal, neuropathic, and CVD risk screenings; and risk screening by blood/urine studies. DR was classified as none (No DR, 37%), mild nonproliferative (Mild DR, 46%), and more than mild NPDR (Advanced DR, 17%). More severe DR was associated with greater age, T1D duration, A1c, and weight status (Table). DR severity was associated with neuropathy, vascular stiffness by pulse wave (aortic AIx), and inflammatory, oxidative stress, and endothelial activation markers (CRP, isoprostane, e-selectin). Paradoxically, greater DR was associated with less PAI-1. After adjustment for age, T1D duration, weight, and A1c by ANCOVA, DR status was associated with differences in cooling threshold (7.6, 8.6, 12.3, p=.0003) and e-selectin (39.8, 34.0, 46.0, p=.02). Young persons with DR have high risk for neuropathic, renal, and CVD complications. While PAI-1 is lower, markers of inflammation and oxidative stress are higher in this group. Optimal glycemic control must be prioritized to prevent or delay DR progression and other complications in young persons with DR. Unadjusted Associations Between Clinical Factors and DR Status, *indicates ln transformed p valueClinical FactorNo DR (n=47) Mean or Median or %Mild DR (n=59) Mean or Median or %Advanced DR (n=21) Mean or Median or %P value ANOVA or Chi-squareAge (yrs)/T1D Duration (yrs)/A1c (%)18.9/13.2/8.022.6/15.8/8.625.8/19.6/9.1&amp;lt;.0001/&amp;lt;.0001/.03Sex (% male)/Overweight/obese (%)60/3236/6148/57.05/.009Urinary Albumin Excretion* /eGFR per 1.73m27.3/128.26.4/141.29.3/140.6.04/.02Neuropathy (MNSI)/Warm Threshold/Cold Threshold1.3/14.6/7.11.9/15.3/8.63.0/18.2/13.4.004/.005/&amp;lt;.001Mean SBP/Mean DBP/Aortic AIx110/68/2.0112/71/9.0115/74/11.1.2/.008/.003PAI1* (ng/ml)/CRP* (mg/l)/IGF1 (ng/ml)36.8/0.8/207.526.2/2.5/160.614.4/2.7/138.8&amp;lt;.001/.002/.002E-selectin(ng/ml)/Urine isoprostane* (ng/ml)40.8/0.2034.5/0.3441.8/0.40.1/.002 Disclosure M. Katz: None. G.L. King: Research Support; Self; Sanofi-Aventis. J. Sun: Other Relationship; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Genentech, Inc., Optovue, Incorporated, Boston Micromachines Corporation, Adaptive Sensory Technology, Kalvista Pharmaceuticals, Inc.. Other Relationship; Self; Novo Nordisk Inc. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson &amp; Johnson Diabetes Institute, LLC..
Mixed Ligated Tris(amidinate)dimolybdenum Complexes as Catalysts for Radical Addition of CCl<sub>4</sub> to 1-Hexene: Leaving Ligand Lability Controls Catalyst Activity (2016)

We synthesized a series of mixed ligated tris(amidinate)dimolybdenum complexes, namely, [Mo<sub>2</sub>(DAniF)<sub>3</sub>(L)] [DAniF = N,N'-di(p-anisyl)formamidinate; L = acetate (OAc; 1a), m-diphenylphosphino benzoate (m-PPh<sub>2</sub>Bz; 1b), nicotinate (Nico; 1c), benzoate (Bz; 1d), 3-furoate (3-Furo; 1e), isonicotinate (IsoNico; 1f), and trifluoromethanesulfonate (OTf; 1g)], which served as catalysts for radical addition of CCl<sub>4</sub> to 1-hexene to give 1,1,1,3-tetrachloroheptane. These mixed ligated complexes 1a-g afforded the higher yield of the radical addition product than a homoleptic DAniF complex, [Mo<sub>2</sub>(DAniF)<sub>4</sub>] (2). Among them, complexes 1a and 1g gave the radical addition product quantitatively after 9 h with a short induction period. When complexes 1a and 1g were treated with CCl<sub>4</sub>, we detected the mixed-valence Mo<sub>2</sub>(II/III) complex, [Mo<sub>2</sub>(DAniF)<sub>3</sub>Cl<sub>2</sub>] (4), in electrospray ionization mass spectrometry measurements, indicating that the leaving nature of the L ligands was a crucial factor for initiating the catalytic reaction: the catalytic activity of the carboxylate-bridged complex 1a and the triflate-bridged complex 1g in the initial 30 min highly depended on the ligand-exchange rate of L, as estimated by monitoring the reaction with CCl<sub>4</sub> in pyridine, giving the pyridine adduct complex, [Mo<sub>2</sub>(DAniF)<sub>3</sub>Cl(py)] (3).
Self-organizing primitives for automated shape composition (2008)

Motivated by the ability of living cells to form into specific shapes and structures, we present a new approach to shape modeling based on self-organizing primitives whose behaviors are derived via genetic programming. The key concept of our approach is that local interactions between the primitives direct them to come together into a macroscopic shape. The interactions of the primitives, called Morphogenic Primitives (MP), are based on the chemotaxis-driven aggregation behaviors exhibited by actual living cells. Here, cells emit a chemical into their environment. Each cell responds to the stimulus by moving in the direction of the gradient of the cumulative chemical field detected at its surface. MPs, though, do not attempt to completely mimic the behavior of real cells. The chemical fields are explicitly defined as mathematical functions and are not necessarily physically accurate. The explicit mathematical form of the chemical field functions are derived via genetic programming (GP), an evolutionary computing process that evolves a population of functions. A fitness measure, based on the shape that emerges from the chemical-field-driven aggregation, determines which functions will be passed along to later generations. This paper describes the cell interactions of MPs and the GP-based method used to define the chemical field functions needed to produce user-specified shapes from simple aggregating primitives.
Discovery of a Novel Series of Pyridone-Based EP3 Antagonists for the Treatment of Type 2 Diabetes (2021)

A novel series of pyridones were discovered as potent EP3 antagonists. Optimization guided by EP3 binding and functional assays as well as by eADME and PK profiling led to multiple compounds with good physical properties, excellent oral bioavailability, and a clean in vitro safety profile. Compound <b>13</b> was identified as a lead compound as evidenced by the reversal of sulprostone-induced suppression of glucose-stimulated insulin secretion in INS 1E β-cells in vitro and in a rat ivGTT model in vivo. A glutathione adduction liability was eliminated by replacing the naphthalene of structure <b>13</b> with the indazole ring of structure <b>43</b>.
&lt;title&gt;Novel approach to color cast detection and removal in digital images&lt;/title&gt; (1999)

Digital Still Camera images often have undesired color casts due to unusual illuminant sources. This paper describes a novel color correction technique that uses adaptive segmentation techniques to identify the presence of such casts, estimate their chromatic strength, and alter the image's near-neutral color regions to compensate for the cast. The segmentation method identifies most major objects in the scene and their average color.
Cell Selective Cardiovascular Biology of Microsomal Prostaglandin E Synthase-1 (2012)

Deletion of mPGES-1 in the vasculature and myeloid cells differentially modulates the response to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target.
Association of molecular subtypes with pathologic response in a phase II study of co-expression extrapolation (COXEN) with neoadjuvant chemotherapy (NAC) for localized, muscle-invasive bladder cancer (SWOG S1314; NCT02177695). (2020)

5028 Background: Cisplatin-based NAC is recommended for patients with MIBC prior to radical cystectomy (RC) but the majority will not have a pathologic response. To identify responders the COXEN gene expression model with chemotherapy-specific scores (for DD-MVAC and GC) was developed and in a prospective rPII clinical trial (SWOG S1314) the GC score was associated with path downstaging in the pooled arms. We investigated RNA based molecular subtypes as additional predictive biomarkers for response to NAC in patients treated in S1314. Methods: Eligibility required cT2-T4a N0 M0, predominant urothelial, &gt; 5 mm tumor, cisplatin eligible, and plan for RC and PLND. 237 patients were randomized between 4 cycles of ddMVAC and GC. Based on Affymetrix transcriptomic data used to assign COXEN scores, we determined subtypes using 3 classifiers: TCGA (k=5), Consensus (k=6), and MD Anderson (MDA; k=3). Primary objective was to assess subtype association with pathologic response to NAC in the pooled arms and to determine any association with COXEN. TCGA and Consensus classifiers were collapsed into 3 groups for ROC analyses. We tested whether each classifier contributed additional predictive power when added to a model based on pre-defined stratification factors (PS 0 vs. 1; T2 vs. T3, T4a). Results: 161 patients had adequate tissue and gene expression results, received at least 3 of 4 cycles of NAC and had pT-N response based on RC. Covariates were 78% PS=0, 89% T2, 84% male, median age 65, 51% randomized to ddMVAC, 49% GC with 33% pT0 and 52% downstaging. Although the TCGA 3 group classifier (Basal-Squamous (BS)/Neuronal, Luminal, Luminal infiltrated) and GC Coxen score yielded the largest AUCs (0.607, 0.610) for pT0 response, neither reached statistical significance (p=0.20, p=0.22). For downstaging (&lt;pT2), the 3 category Consensus classifier (BS/NE-like, Luminal, Stroma-rich) significantly increased the AUC from 0.568 (strat factors alone) to 0.620 (p=0.044). The MDA classifier AUC was 0.640 and the GC Coxen score AUC was 0.626, but neither were significant (p=0.076, p=0.14. The MVAC Coxen score did not improve the AUC beyond the stratification factors. Conclusions: The Consensus classifier, which is based in part on the TCGA and MDA classifiers, modestly improved prediction for pathologic downstaging when added to clinical stage and PS. With additional followup, we will assess the association of COXEN scores and subtypes with overall survival. Clinical trial information: NCT02177695 .
Porcine brain natriuretic peptide, another modulator of bovine adrenocortical steroidogenesis (1988)

Porcine brain natriuretic peptide (pBNP) significantly inhibited aldosterone production stimulated by an angiotensin II analog and ACTH-stimulated cortisol secretion, together with simultaneously increasing the formation of cGMP in dispersed bovine adrenocortical cells. Receptors for pBNP were identified in bovine adrenal gland using an in vitro receptor autoradiographic technique and studies of 125I-pBNP binding. In vitro receptor autoradiography demonstrated specific binding sites for 125I-pBNP in bovine adrenal cortex. Complete displacement of 125I-pBNP by unlabeled pBNP or human atrial natriuretic peptide (hANP) can take place at these sites. Analysis of 125I-pBNP binding to bovine adrenocortical membrane fractions showed that the adrenal cortex had high-affinity, low-capacity pBNP-binding sites, with a dissociation constant (Kd) of 2.32 +/- 0.33 x 10(-10) M (mean +/- SE) and a maximal binding capacity (Bmax) of 36.7 +/- 1.6 fmol/mg protein. Moreover, the specific binding sites for 125I-pBNP were completely displaced not only by unlabeled pBNP but also by unlabeled hANP. The hANP dose required for 50% inhibition of specific 125I-pBNP binding was almost identical to that for pBNP (IC50 values for hANP and pBNP: 8.5 x 10(-10) and 6.5 x 10(-10) M, respectively). These results suggest that pBNP exerts a suppressive effect on bovine adrenocortical steroidogenesis via a receptor which may be shared with ANP.
Alfvén continuum with toroidicity (1986)

The symmetry property of the magnetohydrodynamic (MHD) wave propagation operator is utilized to express the toroidal eigenmodes as a superposition of the mutually orthogonal cylindrical modes. Because of the degeneracy among cylindrical modes with the same frequency but resonant surfaces of different helicity, the toroidal perturbation produces a zeroth-order mixing of the above modes. The toroidal eigenmodes of frequency ω20 have multiple resonant surfaces, with each surface shifted relative to its cylindrical position and carrying a multispectral content. Thus a single helicity toroidal antenna of frequency ω0 couples strongly to all different helicity resonant surfaces with matching local Alfvén frequency. Zeroth-order coupling between modes in the continuum and global Alfvén modes also results from toroidicity and degeneracy. The perturbation technique used in this study is the MHD counterpart of the quantum-mechanical methods and is applicable through the entire range of the MHD spectrum.
Comparison of the performance of innovative deep learning and classical methods of machine learning to solve industrial recognition tasks (2019)

Artificial intelligence and machine learning are becoming increasingly important in science and society. In image processing, they are mainly used for object classification. The aim of this paper is the comparison of classical supervised machine learning methods with innovative deep learning (DL) approaches in terms of performance, which is described by the calculated accuracy. Classifiers of different characteristics are used. These are the Support Vector Machines, Random Forest, k-Nearest-Neighbor, and Naive Bayes. They are compared to two not pre-trained and four pre-trained neural networks. The former neural network are based on LeNet, the second ones include AlexNet, GoogleNet and ResNet provided by Matlab as well as a pre-trained neural network provided by MVTec HALCON. Comparisons were made using the recognition rates achieved with five real data sets from industrial applications. The results showed that not pre-trained neural networks produce worse results than classical classifiers with the given small amounts of data for training. On the other hand, the pre-trained networks achieved surpassing recognition rates. However, if there are features that describe the classes very well, the recognition performance of classical machine learning methods little differs from that of deep learning algorithms.
Interferon-γ Is a Crucial Activator of Early Host Immune Defense against Mycobacterium ulcerans Infection in Mice (2016)

Buruli ulcer (BU), caused by infection with Mycobacterium ulcerans, is a chronic necrotizing human skin disease associated with the production of the cytotoxic macrolide exotoxin mycolactone. Despite extensive research, the type of immune responses elicited against this pathogen and the effector functions conferring protection against BU are not yet fully understood. While histopathological analyses of advanced BU lesions have demonstrated a mainly extracellular localization of the toxin producing acid fast bacilli, there is growing evidence for an early intra-macrophage growth phase of M. ulcerans. This has led us to investigate whether interferon-γ might play an important role in containing M. ulcerans infections. In an experimental Buruli ulcer mouse model we found that interferon-γ is indeed a critical regulator of early host immune defense against M. ulcerans infections. Interferon-γ knockout mice displayed a faster progression of the infection compared to wild-type mice. This accelerated progression was reflected in faster and more extensive tissue necrosis and oedema formation, as well as in a significantly higher bacterial burden after five weeks of infection, indicating that mice lacking interferon-γ have a reduced capacity to kill intracellular bacilli during the early intra-macrophage growth phase of M. ulcerans. This data demonstrates a prominent role of interferon-γ in early defense against M. ulcerans infection and supports the view that concepts for vaccine development against tuberculosis may also be valid for BU.
An ERBB1-3 Neutralizing Antibody Mixture With High Activity Against Drug-Resistant HER2+ Breast Cancers With ERBB Ligand Overexpression (2017)

These data suggest that upregulation of a NRG1-HER3 axis can mediate escape from anti-HER2 therapies. Further, multitargeted antibody mixtures, such as Pan-HER, can simultaneously remove and/or block targeted ERBB receptor and ligands, thus representing an effective approach against drug-sensitive and -resistant HER2+ cancers.
The Majority of Currently Circulating Human Immunodeficiency Virus Type 1 Clade B Viruses Fail To Prime Cytotoxic T-Lymphocyte Responses against an Otherwise Immunodominant HLA-A2-Restricted Epitope: Implications for Vaccine Design (2005)

Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allele in persons infected with clade B virus. Moreover, HLA-A2-restricted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr59-67) that is targeted by acute-phase HIV-1-specific CD8+ T cells, but only in a subset of persons expressing HLA-A2. Individuals in the acute stage of infection with viruses containing the most common current sequence within this epitope (consensus sequence) were unable to mount epitope-specific T-cell responses, whereas subjects infected with the less frequent I60L variant all developed these responses. The I60L variant epitope was a stronger binder to HLA-A2 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope. These data demonstrate that HLA-A2 is capable of contributing to the acute-phase cytotoxic T-lymphocyte response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures.
Extracellular Vesicles in Luminal Fluid of the Ovine Uterus (2014)

Microvesicles and exosomes are nanoparticles released from cells and can contain small RNAs, mRNA and proteins that affect cells at distant sites. In sheep, endogenous beta retroviruses (enJSRVs) are expressed in the endometrial epithelia of the uterus and can be transferred to the conceptus trophectoderm. One potential mechanism of enJSRVs transfer from the uterus to the conceptus is via exosomes/microvesicles. Therefore, studies were conducted to evaluate exosomes in the uterine luminal fluid (ULF) of sheep. Exosomes/microvesicles (hereafter referred to as extracellular vesicles) were isolated from the ULF of day 14 cyclic and pregnant ewes using ExoQuick-TC. Transmission electron microscopy and nanoparticle tracking analysis found the isolates contained vesicles that ranged from 50 to 200 nm in diameter. The isolated extracellular vesicles were positive for two common markers of exosomes (CD63 and HSP70) by Western blot analysis. Proteins in the extracellular vesicles were determined by mass spectrometry and Western blot analysis. Extracellular vesicle RNA was analyzed for small RNAs by sequencing and enJSRVs RNA by RT-PCR. The ULF extracellular vesicles contained a large number of small RNAs and miRNAs including 81 conserved mature miRNAs. Cyclic and pregnant ULF extracellular vesicles contained enJSRVs env and gag RNAs that could be delivered to heterologous cells in vitro. These studies support the hypothesis that ULF extracellular vesicles can deliver enJSRVs RNA to the conceptus, which is important as enJSRVs regulate conceptus trophectoderm development. Importantly, these studies support the idea that extracellular vesicles containing select miRNAs, RNAs and proteins are present in the ULF and likely have a biological role in conceptus-endometrial interactions important for the establishment and maintenance of pregnancy.
The Practice of Nutrition Risk Screening, Nutrition Status Assessment, and Nutrition Support Action (NRASA) in Hospitalized Patients (2023)

The aim of this study was to investigate the prevalence of nutritional risk and malnutrition through the Nutrition Risk Screening, Nutrition Status Assessment, and Nutrition Support Action (NRASA) protocol. A total of 325 140 patients were screened, and 59 122 adults (19.31%) and 9154 children (48.38%) were considered to be “at nutritional risk.” The prevalence of nutritional risk was 18.60% (306 220 patients) based on Nutritional Risk Screening 2002 (NRS2002), and 95.62% (2687 patients) by the Mini-Nutritional Assessment Short-Form (MNA-SF). Almost 67% of 23 805 adult patients were identified to be malnourished. The prevalence of malnutrition was 47.34% (6227 patients) based upon the Subjective Global Assessment (SGA), 69.86% (2687 patients) by the Mini-Nutritional Assessment (MNA) and 97.92% (7689 patients) by the Patient-Generated Subjective Global Assessment (PG-SGA). The NRASA protocol showed that the nutritional care process can be successfully implemented to confer adequate and timely nutritional therapy for malnourished patients.
SC-Explorer: Incremental 3D Scene Completion for Safe and Efficient Exploration Mapping and Planning (2022)

Exploration of unknown environments is a fundamental problem in robotics and an essential component in numerous applications of autonomous systems. A major challenge in exploring unknown environments is that the robot has to plan with the limited information available at each time step. While most current approaches rely on heuristics and assumption to plan paths based on these partial observations, we instead propose a novel way to integrate deep learning into exploration by leveraging 3D scene completion for informed, safe, and interpretable exploration mapping and planning. Our approach, SC-Explorer, combines scene completion using a novel incremental fusion mechanism and a newly proposed hierarchical multi-layer mapping approach, to guarantee safety and efficiency of the robot. We further present an informative path planning method, leveraging the capabilities of our mapping approach and a novel scene-completion-aware information gain. While our method is generally applicable, we evaluate it in the use case of a Micro Aerial Vehicle (MAV). We thoroughly study each component in high-fidelity simulation experiments using only mobile hardware, and show that our method can speed up coverage of an environment by 73% compared to the baselines with only minimal reduction in map accuracy. Even if scene completions are not included in the final map, we show that they can be used to guide the robot to choose more informative paths, speeding up the measurement of the scene with the robot's sensors by 35%. We validate our system on a fully autonomous MAV, showing rapid and reliable scene coverage even in a complex cluttered environment. We make our methods available as open-source.
Maritime route of colonization of Europe (2014)

The Neolithic populations, which colonized Europe approximately 9,000 y ago, presumably migrated from Near East to Anatolia and from there to Central Europe through Thrace and the Balkans. An alternative route would have been island hopping across the Southern European coast. To test this hypothesis, we analyzed genome-wide DNA polymorphisms on populations bordering the Mediterranean coast and from Anatolia and mainland Europe. We observe a striking structure correlating genes with geography around the Mediterranean Sea with characteristic east to west clines of gene flow. Using population network analysis, we also find that the gene flow from Anatolia to Europe was through Dodecanese, Crete, and the Southern European coast, compatible with the hypothesis that a maritime coastal route was mainly used for the migration of Neolithic farmers to Europe.