gebhart/patrepeval huggingface dataset:
Between two worlds: a comparative study on in vitro and in silico inhibition of trypsin and matriptase by redox-stable SFTI-1 variants at near physiological pH (2012)

A comparative study on in vitro and in silico inhibition of trypsin and matriptase by derivatives of the sunflower trypsin inhibitor-1 at near physiological pH is reported. Besides wild-type bicyclic SFTI-1, monocyclic variants possessing native cystine as well as redox-stable triazolyl side-chain macrocyclization motifs were studied for the first time in matriptase inhibition assays. Interestingly, monocyclic SFTI-1[1,14] demonstrated higher potency against this pharmacologically relevant protease compared to its bicyclic counterpart. Structural analysis of binding/inhibition of investigated SFTI-1 derivatives was performed using a combination of molecular dynamics simulations and docking experiments. In silico data were in good accordance with in vitro results, indicating the importance of the terminal inhibitor regions for the affinity towards matriptase. Presented work gives new perspectives for the optimization of the SFTI-1 framework towards in vivo applications.
P4–345: Providing standardized labels of the EADC‐ADNI Harmonized Hippocampal Protocol for automated algorithm training (2013)

The EADC-ADNI Harmonized Protocol (HP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance images (MRI). The project produced benchmark, standardized labels enabling training and qualification of future human tracers. However, training automated segmentation algorithms requires larger datasets representative of wider physiological variability. This work aims to produce a set of standardized labels allowing proper training of automated segmentation algorithms. We selected 135 ADNI images from different subjects, balanced by diagnosis, degree of medial temporal atrophy (Scheltens' visual scale, 1992), scanner type, magnet field strength, and age. We recruited tracers among HP segmentation experts based on excellent tracing performance as judged by volume ICC>0.94 or Jaccard>0.82 (Figure). We certified standardized labels as HP-compliant after centralized quality checks and corrections. Internal hippocampal CSF spaces were separately labelled, and excluded from hippocampal volume. We run t-tests and correlation analyses to evaluate volume differences across diagnoses and medial temporal atrophy. We have completed segmentations, double step quality check, corrections and final certification for N=68 subjects at 1.5T MRIs, with a single tracer. Uncorrected hippocampal volumes of patients differed significantly from controls: AD patients had 19% smaller volumes than controls (left: mm 3 2386, SD=510, p=0.001, right: 2427 SD=568, p=0.001); MCI had 14% smaller volumes than controls (left: 2576, SD=521, p=0.026, right: 2550 SD=614, p=0.013); Controls: left 2953, SD=590, right: 2994 SD=537. These raw volumes significantly correlated with atrophy severity at Scheltens' scale (Table).CSF spaces were larger in controls: AD, left: mm 3 16, SD=16, p=0.036, right: 31, SD=30, p=0.074; MCI, left: 17, SD=9, p=0.033, right: 29, SD=16, p=0.102; Controls, left, 34 SD=35, right: 34 SD=37. Two subjects (3%) presented with unusual anatomy. Example of compliance with the Harmonized Protocol, required to a new tracer to be a tracer for the Harmonized Benchmark Labels. In this case, the tracer had a Jaccard index of 0.87 with the mean contour of the benchmark labels provided by the Harmonized Protocol project.
Molecular Pathogenesis of EBV Susceptibility in XLP as Revealed by Analysis of Female Carriers with Heterozygous Expression of SAP (2011)

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency caused by mutations in SH2D1A which encodes SAP. SAP functions in signalling pathways elicited by the SLAM family of leukocyte receptors. A defining feature of XLP is exquisite sensitivity to infection with EBV, a B-lymphotropic virus, but not other viruses. Although previous studies have identified defects in lymphocytes from XLP patients, the unique role of SAP in controlling EBV infection remains unresolved. We describe a novel approach to this question using female XLP carriers who, due to random X-inactivation, contain both SAP(+) and SAP(-) cells. This represents the human equivalent of a mixed bone marrow chimera in mice. While memory CD8(+) T cells specific for CMV and influenza were distributed across SAP(+) and SAP(-) populations, EBV-specific cells were exclusively SAP(+). The preferential recruitment of SAP(+) cells by EBV reflected the tropism of EBV for B cells, and the requirement for SAP expression in CD8(+) T cells for them to respond to Ag-presentation by B cells, but not other cell types. The inability of SAP(-) clones to respond to Ag-presenting B cells was overcome by blocking the SLAM receptors NTB-A and 2B4, while ectopic expression of NTB-A on fibroblasts inhibited cytotoxicity of SAP(-) CD8(+) T cells, thereby demonstrating that SLAM receptors acquire inhibitory function in the absence of SAP. The innovative XLP carrier model allowed us to unravel the mechanisms underlying the unique susceptibility of XLP patients to EBV infection in the absence of a relevant animal model. We found that this reflected the nature of the Ag-presenting cell, rather than EBV itself. Our data also identified a pathological signalling pathway that could be targeted to treat patients with severe EBV infection. This system may allow the study of other human diseases where heterozygous gene expression from random X-chromosome inactivation can be exploited.
The C4b-binding Protein-Protein S Complex Inhibits the Phagocytosis of Apoptotic Cells (2004)

The phagocytosis of apoptotic cells is a complex process involving numerous interactions between the target cell and the macrophage. We have examined a role of the major soluble inhibitor of the classic and lectin complement pathways, C4b-binding protein (C4BP), in the clearance of apoptotic cells. The major form of C4BP present in blood is composed of seven alpha-chains and one beta-chain, which binds protein S (PS). Approximately 70% of all PS in human plasma is trapped in such a complex and is able to localize C4BP to the surface of apoptotic cells due to the high affinity to phosphatidylserine. Free PS has recently been shown to enhance phagocytosis of apoptotic cells by macrophages. We observed a stimulatory effect of free PS on the engulfment of apoptotic cells (BL-41 and Jurkat) by primary human macrophages or THP-1 cells and a decrease of activity in serum depleted of PS in agreement with previous results. However, we also show that the process is strongly inhibited in the presence of the C4BP-PS complex. Addition of the C4BP-PS complex to serum deficient in both molecules abolished the enhancing effect of serum on phagocytosis. The effect of both free PS and the C4BP-PS complex could be inhibited with monoclonal antibody directed against the Gla domain of PS. Although the presence of the C4BP-PS complex on apoptotic cells may lead to decreased phagocytosis, it may still be beneficial to the host, since it could prevent secondary necrosis because it inhibits further complement attack.
Type IX collagen deficiency enhances the binding of cartilage-specific antibodies and arthritis severity (2006)

Joint cartilage is attacked in both autoimmune inflammatory and osteoarthritic processes. Type IX collagen (CIX) is a protein of importance for cartilage integrity and stability. In this study we have backcrossed a transgenic disruption of the col9a1 gene, which leads to an absence of CIX, into two different inbred mouse strains, DBA/1 and B10.Q. None of the CIX-deficient mice developed observable clinical or microscopic osteoarthritis, but DBA/1 male mice had more pronounced enthesopathic arthritis, the so-called stress-induced arthritis. Both DBA/1 and B10.Q strains are susceptible to the induction of collagen-induced arthritis, and CIX deficiency in both strains led to the development of a more severe arthritis than in the controls. Induction of arthritis with monoclonal antibodies against type II collagen (CII) led to an earlier arthritis in the paws that also involved the knee joints. The antibodies used, which were specific for the J1 and the C1I epitopes of CII, initiate their arthritogenic attack by binding to cartilage. The C1I-specific antibodies bound to cartilage better in CIX-deficient mice than in wild-type animals, demonstrating that the lack of CIX in cartilage leads to an increased accessibility of structures for antibody binding and thus making the joints more vulnerable to inflammatory attack. These findings accentuate the importance of cartilage stability; cartilage disrupted as a result of genetic disorders could be more accessible and vulnerable to an autoimmune attack by pathogenic antibodies.
Control of a Dual-Stator Flux-Modulated Motor for Electric Vehicles (2016)

This paper presents the control strategies for a novel dual-stator flux-modulated (DSFM) motor for application in electric vehicles (EVs). The DSFM motor can be applied to EVs because of its simple winding structure, high reliability, and its use of two stators and rotating modulation steels in the air gap. Moreover, it outperforms conventional brushless doubly-fed machines in terms of control performance. Two stator-current-oriented vector controls with different excitation in the primary winding, direct and alternating current excitation, are designed, simulated, and evaluated on a custom-made DSFM prototype allowing the decoupled control of torque. The stable speed response and available current characteristics strongly validate the feasibility of the two control methods. Furthermore, the proposed control methods can be employed in other applications of flux-modulated motors.
Is High-Grade Prostate Cancer Easier to Find in Smaller Prostates Because There Is More High-Grade Disease to Find? – Letter (2010)

Elliott et al. (1) report that prostate-specific antigen (PSA) performance was significantly better in identifying high-grade disease in men with smaller prostates. They use this observation to support the hypothesis that the increased detection of high-grade disease in the finasteride arm of the Prostate Cancer Prevention Trial was due to an artifact in which the reduction in prostate size made it possible for PSA testing to identify the cancer better in smaller prostates. In their analysis, however, they do not consider another explanation for their findings.It is well established that patients with smaller prostates have more high-grade disease, more extraprostatic extension with positive surgical margins, and higher rates of biochemical progression following radical prostatectomy than men with larger prostates (2–4). Simply stated, did the authors find more high-grade cancer in smaller prostates because there was more high-grade disease to find and not because PSA was better at finding it? Although PSA may perform better in the absence of prostatic enlargement, when Freedland et al. (2) excluded men with T1c disease and examined only men who had abnormal digital rectal examinations, they found that the association between smaller prostate size, higher grade advanced disease, and biochemical progression remained statistically significant. In the authors' study, 39% of their patients were also diagnosed with palpable disease and those men with smaller prostates also had higher rates of Gleason 7 to 10 disease and higher PSA density (PSA divided by prostate volume). If so, how does this help explain the Prostate Cancer Prevention Trial findings as an artifact? If high-volume, high-grade disease was detected more often during the first 7 years in the finasteride arm, then one would assume eventually over time that there would be fewer patients with high-grade disease. Instead, at 7 years, there were almost twice as many high-grade cancers in the finasteride arm, and in the end of study biopsies, the number was the same, not fewer (5). The authors are at an institution that has emphasized the value of measuring tumor volume in radical prostatectomy specimens and may be able to determine if the volume of high-grade tumor in the smaller prostates was the same as in larger prostates. This would support their conclusion. If not, how is this an artifact?No potential conflicts of interest were disclosed.
Static Stability of Robotic Fabric Strip Folding (2020)

Planning accurate manipulation of deformable objects requires the ability to predict their state. Prediction is often complicated by a loss of stability that can result in the collapse of a deformable object. This article studies the stability of fabric strip folding performed by a robot. We show that a static instability exists in the folding process. This instability is detected in a physics-based simulation, and the position of the instability is experimentally verified for various fabric materials during robotic manipulation. Three state-of-the-art methods for folding are assessed in the presence of static instability. It is shown that one of the existing folding paths is suitable for the folding of materials with internal friction, such as fabrics. A folding path that utilizes dynamic motion exists for ideal elastic materials without internal friction. Our results show that instability needs to be considered during the planning phase in order to ensure accurate manipulation of deformable objects.
Plant Phenolics Inhibit Neutrophil Elastase (2006)

Human neutrophil elastase (HNE) is a serine protease, which is present in its active form in inflamed tissue as well as in psoriatic lesions. In extension of our research on natural compounds as inhibitors of HNE or of its release, several phenolics of different size were tested. The ellagitannins agrimoniin and pedunculagin were the most potent direct HNE inhibitors (IC (50) = 0.9 and 2.8 microM, respectively). Ligand docking calculations provided evidence that inhibition may occur in an unspecific manner. Agrimoniin also showed anti-proliferative effects in the ATP assay (IC (50) = 3.2 microM), suggesting that this type of tannin could have beneficial effects in the treatment of diseases such as psoriasis. Tests with other phenolics combined with ligand docking experiments revealed that, besides the presence of ORTHO-dihydroxy groups, a specific lipophilic shape is necessary for an inhibitory activity. The phenolic genistein deserves special interest as an inhibitor of elastase release because its effect was remarkably potent (IC (50) = 0.6 microM).
Intensive Diagnostic Follow-up After Treatment of Primary Breast Cancer (1994)

Objective. —To evaluate the effectiveness of early detection of intrathoracic and bone metastases in reducing mortality in breast cancer patients. Design. —Randomized clinical trial allocating breast cancer patients to two alternative follow-up protocols (intensive vs clinical) for at least 5 years. Setting. —Twelve breast clinics (referral centers) in different areas in Italy. Patients. —A total of 1243 consecutive patients (either premenopausal or postmenopausal) surgically treated for unilateral invasive breast carcinoma with no evidence of metastases. The two study groups were well balanced in terms of clinical and prognostic characteristics. Intervention. —Patients in both treatment groups had physical examination and mammography, while patients of the intensive follow-up group had, in addition, chest roentgenography and bone scan every 6 months. Main Outcome Measures. —Vital status at 5 years was the main outcome; information was available for all except five patients (0.4%). Relapse-free survival was also analyzed. Results. —Overall, 393 recurrences (104 local and 289 distant) were observed during the study. Increased detection of isolated intrathoracic and bone metastases was evident in the intensive follow-up group compared with the clinical follow-up group (112 vs 71 cases), while no difference was observed for other sites and for local and/or regional recurrences. The 5-year relapse-free survival rate was significantly higher for the clinical follow-up group, with patients in the intensive follow-up group showing earlier detection of recurrences. No difference in 5-year overall mortality (18.6% vs 19.5%) was observed between the two follow-up groups. Conclusions. —Periodic chest roentgenography and bone scan allow earlier detection of distant metastases, but anticipated diagnosis appears to be the only effect of intensive follow-up, and no impact on prognosis is evident after 5 years. Periodic intensive follow-up with chest roentgenography and bone scan should not be recommended as a routine policy. (JAMA. 1994;271:1593-1597)
Data from Plasma MicroRNAs as Novel Biomarkers for Endometriosis and Endometriosis-Associated Ovarian Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Endometriosis, a largely benign, chronic inflammatory disease, is an independent risk factor for endometrioid and clear cell epithelial ovarian tumors. We aimed to identify plasma miRNAs that can be used to differentiate patients with endometriosis and ovarian cancer from healthy individuals.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We conducted a two-stage exploratory study to investigate the use of plasma miRNA profiling to differentiate between patients with endometriosis, patients with endometriosis-associated ovarian cancer (EAOC), and healthy individuals. In the first stage, using global profiling of more than 1,000 miRNAs via reverse transcriptase quantitative PCR (RT-qPCR) in a 20-patient initial screening cohort, we identified 23 candidate miRNAs, which are differentially expressed between healthy controls (&lt;i&gt;n&lt;/i&gt; = 6), patients with endometriosis (&lt;i&gt;n&lt;/i&gt; = 7), and patients with EAOC (&lt;i&gt;n&lt;/i&gt; = 7) based on the fold changes. In the second stage, the 23 miRNAs were further tested in an expanded cohort (&lt;i&gt;n&lt;/i&gt; = 88) of healthy individuals (&lt;i&gt;n&lt;/i&gt; = 20), endometriosis (&lt;i&gt;n&lt;/i&gt; = 33), EAOC (&lt;i&gt;n&lt;/i&gt; = 14), and serous ovarian cancer cases (SOC; &lt;i&gt;n&lt;/i&gt; = 21, included as controls).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We identified three distinct miRNA signatures with reliable differential expression between healthy individuals, patients with endometriosis, and patients with EAOC. When profiled against the control SOC category, our results revealed different miRNAs, suggesting that the identified signatures are reflective of disease-specific pathogenic mechanisms. This was further supported by the fact that the majority of miRNAs differentially expressed in human EAOCs were mirrored in a double transgenic mouse EAOC model.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Our study reports for the first time that distinct plasma miRNA expression patterns may serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis, and EAOC cases. &lt;i&gt;Clin Cancer Res; 19(5); 1213–24. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Frequency Division Multiplexed Recording of Analog/Digital Signals in the TAT System. (1994)

This paper discusses the frequency division multiplexed VCR recording of a bandwidth
Diamond-based composite layers as protective coatings for ion beam extraction systems (2001)

W-containing polycrystalline diamond films were produced by a hybrid chemical vapor deposition- powder flowing technique, in order to test the feasibility of using composite diamond-based materials as protective coatings for acceleration grids subjected to ion bombardment. The morphology and structure of the composite layers, deposited on Mo substrates, were investigated by scanning electron microscopy and reflection high-energy electron diffraction. It is found that W insertion substantially lowers the resistivity of the diamond-based layers (around 10−2Ω cm) but does not modify the lattice parameters of the host diamond matrix. The performance of such coatings for shielding Mo grids from ion-induced sputtering was tested using 1 keV Ar+ beams. The Auger electron spectroscopy spectra indicated that the dose of 6×1019 ions/cm2 employed was not sufficient for complete erosion of the composite layers, for which sputtering yields in the range of 0.6–0.9 atoms/ion were measured. The secondary electron emission induced by 1.5–4.0 keV Ar+ ions was investigated and compared with the emission from uncoated Mo samples.
Alteration of autonomic blood pressure control during hemodialysis in peripheral vascular disease patients (2011)

Blood pressure (BP) response to volume depletion induced by hemodialysis (HD) treatment may be important to understand the pathophysiology of the increased mortality in HD patients with vascular calcification. In the present study a comparison between end stage renal disease (ESRD) patients affected by peripheral vascular disease (PVD) and ESRD patients without PVD was performed. Continuous blood pressure was recorded at the beginning and at the end of HD. BP and heart rate variability (HRV) were analyzed to quantify the autonomic nervous system regulation of heart beat and peripheral resistance. PVD patients showed an increase of pulse pressure (PP) during HD, an altered autonomic peripheral control, a lower sympathetic activity, with respect to ESRD patients without PVD.
Supplementary Data from BRD9 Is a Critical Regulator of Androgen Receptor Signaling and Prostate Cancer Progression (2023)

&lt;p&gt;Figures S1-S6&lt;/p&gt;
Electric-field sensing near the surface microstructure of an atom chip using cold Rydberg atoms (2012)

The electric fields near the heterogeneous metal-dielectric surface of an atom chip were measured using cold atoms. The atomic sensitivity to electric fields was enhanced by exciting the atoms to Rydberg states that are 10${}^{8}$ times more polarizable than the ground state. We attribute the measured fields to charging of the insulators between the atom chip wires. Surprisingly, it is found that although the chip wire currents were turned off before Rydberg excitation, the measured fields were strongly influenced by how the wire currents had been applied. These fields may be dramatically lowered with appropriate voltage biasing, suggesting configurations for the future development of hybrid quantum systems.
Influence of Relative Dip Angle and Bed Thickness on LWD Density Images Acquired in High-Angle and Horizontal Wells (2009)

This paper describes numerical simulations undertaken to quantify the influence of relative dip angle and bed thickness on LWD density images acquired in high-angle and horizontal (HA/HZ) wells penetrating thinly-bedded formations. Simulations assume a commercial LWD tool as well as commercial count-rate processing. Results indicate that density images can be used to quantify bed thickness, bed density, and relative dip when the thickness of the bed is equal or larger than six inches and relative dip angle is larger than 75°. A field example of LWD instrument response across thinly-bedded formations in a HA/HZ well confirms the reliability of numerical simulations and their value in assessing petrophysical properties of thinly-bedded rock sequences penetrated by HA/HZ wells. Our study also considers alternative processing techniques to estimate bed density and thickness from LWD density measurements acquired in HA/HZ wells.