gebhart/patrepeval huggingface dataset:
Identification of Gene Expression Differences between Lymphangiogenic and Non-Lymphangiogenic Non-Small Cell Lung Cancer Cell Lines (2016)

It is well established that lung tumors induce the formation of lymphatic vessels. However, the molecular mechanisms controlling tumor lymphangiogenesis in lung cancer have not been fully delineated. In the present study, we identify a panel of non-small cell lung cancer (NSCLC) cell lines that induce lymphangiogenesis and use genome-wide mRNA expression to characterize the molecular mechanisms regulating tumor lymphangiogenesis. We show that Calu-1, H1993, HCC461, HCC827, and H2122 NSCLC cell lines form tumors that induce lymphangiogenesis whereas Calu-3, H1155, H1975, and H2073 NSCLC cell lines form tumors that do not induce lymphangiogenesis. By analyzing genome-wide mRNA expression data, we identify a 17-gene expression signature that distinguishes lymphangiogenic from non-lymphangiogenic NSCLC cell lines. Importantly, VEGF-C is the only lymphatic growth factor in this expression signature and is approximately 50-fold higher in the lymphangiogenic group than in the non-lymphangiogenic group. We show that forced expression of VEGF-C by H1975 cells induces lymphangiogenesis and that knockdown of VEGF-C in H1993 cells inhibits lymphangiogenesis. Additionally, we demonstrate that the triple angiokinase inhibitor, nintedanib (small molecule that blocks all FGFRs, PDGFRs, and VEGFRs), suppresses tumor lymphangiogenesis in H1993 tumors. Together, these data suggest that VEGF-C is the dominant driver of tumor lymphangiogenesis in NSCLC and reveal a specific therapy that could potentially block tumor lymphangiogenesis in NSCLC patients.
Folding Control and Unfolding Free Energy of Yeast Iso-1-cytochrome c Bound to Layered Zirconium Phosphate Materials Monitored by Surface Plasmon Resonance (2008)

The free energy change (Delta G degrees ) for the unfolding of immobilized yeast iso-1-cytochrome c (Cyt c) at nanoassemblies was measured by surface plasmon resonance (SPR) spectroscopy. Data show that SPR is sensitive to protein conformational changes, and protein solid interface exerts a major influence on bound protein stability. First, Cyt c was self-assembled on the Au film via the single thiol of Cys-102. Then, crystalline sheets of layered alpha-Zr(O(3)POH)(2).H(2)O (alpha-ZrP) or Zr(O(3)PCH(2)CH(2)COOH)(2).xH(2)O (alpha-ZrCEP) were adsorbed to construct alpha-ZrP/Cyt c/Au or alpha-ZrCEP/Cyt c/Au nanoassemblies. The construction of each layer was monitored by SPR, in real time, and the assemblies were further characterized by atomic force microscopy and electrochemical studies. Thermodynamic stability of the protein nanoassembly was assessed by urea-induced unfolding. Surprisingly, unfolding is reversible in all cases studied here. Stability of Cyt c in alpha-ZrP/Cyt c/Au increased by approximately 4.3 kJ/mol when compared to the unfolding free energy of Cyt c/Au assembly. In contrast, the protein stability decreased by approximately 1.5 kJ/mol for alpha-ZrCEP/Cyt c/Au layer. Thus, OH-decorated surfaces stabilized the protein whereas COOH-decorated surfaces destabilized it. These data quantitate the role of specific functional groups of the inorganic layers in controlling bound protein stability.
Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: A report of the 1985–1986 nhlbi ptca registry (1991)

In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985-May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p less than 0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p less than 0.001). Incidence of major patient complications (p less than 0.01) and of emergency coronary bypass surgery (p less than 0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979-1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single- and multi-vessel coronary disease.
Power supply clamp for multi-domain mixed-signal SiGe BiCMOS applications (2013)

An active power supply clamp for precision high speed SiGe BiCMOS applications is introduced. The clamp architecture includes functional blocks for transient stress detection, stress-adapted activation feedback and mistriggering control. Electrostatic discharge (ESD) robustness is demonstrated in high speed/high voltage BiCMOS SiGe applications operating at supply voltages beyond the breakdown voltage constraint in the bipolar signal processing blocks during ESD stress.
Structural and optical characterization of AlGaN multiple quantum wells grown on semipolar (20-21) bulk AlN substrate (2017)

Heterostructures of AlGaN with multiple quantum wells were grown by metal-organic vapor phase epitaxy on semipolar (20-21) bulk AlN substrates. Smooth epitaxial surfaces with excellent heterostructure interfaces were demonstrated. Luminescence from the AlGaN multiple quantum wells emitting at λ = 237 nm show a substantial degree of polarization of about 35% as determined by low-temperature photoluminescence measurements.
Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Suppresses the Humoral and Cell-Mediated Immune Responses to Influenza A Virus without Affecting Cytolytic Activity in the Lung (2000)

The immune response to influenza virus is exquisitely sensitive to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); however, the cellular mechanisms underlying the suppressive effects of TCDD are unknown. Mice exposed to TCDD exhibited a dose-responsive increase in mortality following an otherwise non-lethal influenza virus infection. Given that cytotoxic T lymphocytes (CTL) are generally thought to resolve primary infections in the lung, we tested the hypothesis that exposure to TCDD suppresses T-cell responsiveness, leading to decreased CTL in the lung. After infection with influenza virus, naive CD8+ lymphocytes are activated and differentiate in the mediastinal lymph node (MLN). In mice exposed to TCDD and infected with influenza virus, the number of CD8+ MLN cells was reduced 60% compared to vehicle-treated mice. Moreover, MLN cells from TCDD-treated mice failed to develop cytolytic activity, and the production of interleukin (IL)-2 and interferon (IFN)-gamma was suppressed. Exposure to TCDD also altered the production of virus-specific antibodies, decreased the recruitment of CD8+ cells to the lung, reduced the percentage and number of bronchoalveolar lavage cells bearing a CTL phenotype (CD8+CD44hiCD62L(l) degrees ), and suppressed IL-12 levels in the lung. Despite our findings that exposure to TCDD suppressed T cell-dependent functions, the cytolytic activity of lung lavage cells from TCDD and vehicle treated mice was equivalent, and IFN gamma levels in the lungs of mice treated with TCDD were enhanced 10-fold. Thus, while exposure to TCDD suppressed a number of responses associated with the development of adaptive immunity to influenza virus, a direct link between these effects and enhanced susceptibility to influenza remains unclear.
An Artificial Agent for Anatomical Landmark Detection in Medical Images (2016)

Fast and robust detection of anatomical structures or pathologies represents a fundamental task in medical image analysis. Most of the current solutions are however suboptimal and unconstrained by learning an appearance model and exhaustively scanning the space of parameters to detect a specific anatomical structure. In addition, typical feature computation or estimation of meta-parameters related to the appearance model or the search strategy, is based on local criteria or predefined approximation schemes. We propose a new learning method following a fundamentally different paradigm by simultaneously modeling both the object appearance and the parameter search strategy as a unified behavioral task for an artificial agent. The method combines the advantages of behavior learning achieved through reinforcement learning with effective hierarchical feature extraction achieved through deep learning. We show that given only a sequence of annotated images, the agent can automatically and strategically learn optimal paths that converge to the sought anatomical landmark location as opposed to exhaustively scanning the entire solution space. The method significantly outperforms state-of-the-art machine learning and deep learning approaches both in terms of accuracy and speed on 2D magnetic resonance images, 2D ultrasound and 3D CT images, achieving average detection errors of 1-2 pixels, while also recognizing the absence of an object from the image.
Innate Immunity E To Acquire Human Plasminogen and To Evade Uses the Surface Protein Haemophilus influenzae (2011)

Subscriptionshttp://www.jimmunol.org/subscriptions Information about subscribing to The Journal of Immunology is online atPermissionshttp://www.aai.org/ji/copyright.html Submit copyright permission requests atEmail Alertshttp://www.jimmunol.org/etoc/subscriptions.shtml/ Receive free email-alerts when new articles cite this article. Sign up at
High-field MRS in clinical drug development (2013)

MRS-guided drug discovery is poised for future expansion. The cost of clinical trials has escalated and the use of biomarkers has become increasingly useful in improving patient selection for drug trials. Clinical MRS has uncovered a treasure-trove of novel biomarkers and clinical MRS itself has become better standardized and more widely available on 'routine' clinical MRI scanners. When combined with available new MRI sequences, MRS can provide a 'one stop shop' with multiple potential outcome measures for the disease and the drug in question.
THE PREVALENCE OF RADIOLUCENCY IS REDUCED IN THE OXFORD DOMED LATERAL UNICOMPARTMENTAL KNEE REPLACEMENT (2012)

Introduction Radiolucencies beneath the tibial component are well recognized in knee arthroplasty; the aetiology and significance are poorly understood. Non-progressive narrow radiolucencies with a sclerotic margin are thought not to be indicative of loosening. Factors which decrease the incidence of radiolucencies include cementless fixation and the use of pulse lavage. Leg/component alignment or BMI do not influence radiolucency. We are not aware of any studies that have looked at the effect of load type on radiolucency. The Oxford domed lateral tibial component was introduced to decrease the bearing dislocation rate that was unacceptably high with the flat tibial tray. However, the introduction of the domed tibial component alters the forces transmitted through the implant-cement-bone interface. As the Oxford UKR uses a fully congruent mobile bearing, the forces transmitted through the interface with a flat tray are compressive, except for the effect of friction. However, with the domed tibial component shear forces are introduced. The aim of this study was to assess the prevalence of radiolucency beneath the previous flat design and the new domed tibial tray. Patients and methods A consecutive series of 248 cemented lateral UKRs (1999–2009) at a single institution were assessed. The first 55 were with a flat tibia and the subsequent 193 with a domed component. One year post-op radiographs were assessed, by two observers, for the presence (full or partial) and distribution of radiolucency. The distribution and thickness of each radiolucency. Cases were excluded for missing or poorly aligned radiographs. Results In the flat group there were 42 patients (17 male, 25 female) with 42 joints. In the domed group there were 139 patients (44 male, 95 female) with 146 joints. There was a statistical significant difference between groups for the presence and extent of radiolucency (p Discussion The introduction the domed lateral tibial component results in a reduction in prevalence of radiolucency compared to a flat component. This suggests, as the mode of fixation is identical, that the forces across the tibial-cement-bone interface have a significant effect on the development of the tissue at that interface. In particular it suggests that compressive forces alone tend to cause soft tissue to be formed at the interface, whereas shear force causes bone.
How to coordinate the trade-off between water permeability and salt rejection in nanofiltration? (2020)

Technical principles of coordinating the trade-off between water permeability and salt rejection in NF membranes have been proposed and elaborated.
Data from A Multiantigen Vaccine Targeting Neu, IGFBP-2, and IGF-IR Prevents Tumor Progression in Mice with Preinvasive Breast Disease (2023)

&lt;div&gt;Abstract&lt;p&gt;A multiantigen multipeptide vaccine, targeting proteins expressed in preinvasive breast lesions, can stimulate type I CD4&lt;sup&gt;+&lt;/sup&gt; T cells which have been shown to be deficient in both patients with breast cancer and mice that develop mammary tumors. Transgenic mice (TgMMTV-neu) were immunized with a multiantigen peptide vaccine specific for neu, insulin—like growth factor-binding protein 2 and insulin-like growth factor receptor-I at a time when some of the animals already had preinvasive lesions (18 weeks of age). Although immunization with each individual antigen was partially effective in inhibiting tumor growth, immunization with the multiantigen vaccine was highly effective, blocking development of palpable lesions in 65% of mice and slowing tumor growth in the infrequent palpable tumors, which did arise. Protection was mediated by CD4&lt;sup&gt;+&lt;/sup&gt; T cells, and the few slow-growing tumors that did develop demonstrated a significant increase in intratumoral CD8&lt;sup&gt;+&lt;/sup&gt; T cells as compared with controls (&lt;i&gt;P&lt;/i&gt; = 0.0007). We also combined the vaccine with agents that were, by themselves, partially effective inhibitors of tumor progression in this model; lapatinib and the RXR agonist bexarotene. Although the combination of lapatinib and vaccination performed similarly to vaccination alone (&lt;i&gt;P&lt;/i&gt; = 0.735), bexarotene and vaccination significantly enhanced disease-free survival (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), and approximately 90% of the mice showed no pathologic evidence of carcinomas at one year. The vaccine also demonstrated significant clinical efficacy in an additional transgenic model of breast cancer (TgC3(I)-Tag). Chemoimmunoprevention combinations may be an effective approach to breast cancer prevention even when the vaccine is administered in the presence of subclinical disease. &lt;i&gt;Cancer Prev Res; 6(12); 1273–82. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Adjuvant Effect of Topical Imiquimod Compared to Intradermal GM-CSF on the Cellular Composition of Draining Lymph Nodes (2004)

s for the 19th Annual Scientific Meeting of the International Society for Biological Therapy of Cancer, San Francisco, California, November 4-7, 2004: Immune Adjuvants
Isolation of gravitational waves from displacement noise and utility of a time-delay device (2007)

Interferometers with kilometer-scale arms have been built for gravitational-wave detections on the ground; ones with much longer arms are being planned for space-based detection. One fundamental motivation for long baseline interferometry is from displacement noise. In general, the longer the arm length L, the larger the motion the gravitational-wave induces on the test masses, until L becomes comparable to the gravitational wavelength. Recently, schemes have been invented, in which displacement noises can be evaded by employing differences between the influence of test-mass motions and that of gravitational waves on light propagation. However, in these schemes, such differences only becomes significant when L approaches the gravitational wavelength, and shot-noise limited sensitivity becomes worse than that of conventional configurations by a factor of at least (f L/c)^(-2), for f<c/L. Such a factor, although can be overcome theoretically by employing high optical powers, makes these schemes quite impractical. In this paper, we explore the use of time delay in displacement-noise-free interferometers, which can improve their shot-noise-limited sensitivity at low frequencies, to a factor of (f L/c)^(-1) of the shot-noise-limited sensitivity of conventional configurations.
A rational pre-catalyst design for bis-phosphine mono-oxide palladium catalyzed reactions (2017)

Significant catalyst loading reduction and increased reaction robustness have been achieved for a Pd-catalyzed asymmetric intramolecular C-N coupling through comprehensive mechanistic studies. Detailed kinetic, spectroscopic, and crystallographic analyses revealed that the mono-oxidation of the bis-phosphine ligand is critical for a successful transformation. <sup>31</sup>P NMR studies provided an understanding of the inefficient activation of the Pd(OAc)<sub>2</sub>/(<i>R</i>,<i>R</i>)-QuinoxP* pre-catalyst to form the active bis-phosphine mono-oxide-Pd(0) catalyst with competitive formation of a less active (<i>R</i>,<i>R</i>)-QuinoxP*·PdBr<sub>2</sub> complex. Based on these detailed mechanistic studies, a new series of bis-phosphine mono-oxides (BPMO)-ligated Pd(ii) pre-catalysts have been rationally developed that allow for reliable and complete catalyst activation which should have general utility in academic and industrial settings.
Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome (2019)

Crohn's disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosa-associated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn's-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti-IL-1α administration led to a decreased ratio of <i>Proteobacteria</i> to <i>Bacteroidetes</i>, decreased presence of <i>Helicobacter</i> species, and elevated representation of <i>Mucispirillum schaedleri</i> and <i>Lactobacillus salivarius</i>. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α-based therapies.
A fast method to evaluate the optimum number of spares in defect-tolerant integrated circuits (1994)

We present a method to accelerate the search for the number of spares to be included in defect tolerant integrated circuits. Our method is obtained by bringing two modifications to a conventional evaluation method. The main motivations behind the development of this method are: the possibilities offered by the implementation of defect tolerance, the existence of many yield models, which may predict different results in terms of optimum number of spares, and the fact that some models are very compute intensive. The modeling methods leading to several usual yield models are briefly presented. We also present results showing that our method is valid for a wide range of parameters. However, this method can be applied to all yield models considered and it can significantly reduce the time spent in the search for the best possible reconfiguration strategies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design and Synthesis of High‐Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors (2014)

Abstract Gephyrin is the central scaffolding protein for inhibitory neurotransmitter receptors in the brain. Here we describe the development of dimeric peptides that inhibit the interaction between gephyrin and these receptors, a process which is fundamental to numerous synaptic functions and diseases of the brain. We first identified receptor‐derived minimal gephyrin‐binding peptides that displayed exclusive binding towards native gephyrin from brain lysates. We then designed and synthesized a series of dimeric ligands, which led to a remarkable 1220‐fold enhancement of the gephyrin affinity ( K D =6.8 n M ). In X‐ray crystal structures we visualized the simultaneous dimer‐to‐dimer binding in atomic detail, revealing compound‐specific binding modes. Thus, we defined the molecular basis of the affinity‐enhancing effect of multivalent gephyrin inhibitors and provide conceptually novel compounds with therapeutic potential, which will allow further elucidation of the gephyrin–receptor interplay.
Practical Considerations in the Use of Real-Time Continuous Glucose Monitoring Alerts (2010)

Care should be taken to set CGM alerts at levels that result in a manageable number of notifications per day. In some cases, providers should consider not using alerts at all or consider using broad targets when initiating CGM to maximize alert specificity. Real-time CGM is safe and generally well tolerated; however, individualization of alert settings is necessary maximize the system's benefits and patient adherence.