gebhart/patrepeval huggingface dataset:
Data from Biomarker Analyses from a Placebo-Controlled Phase II Study Evaluating Erlotinib ± Onartuzumab in Advanced Non–Small Cell Lung Cancer: MET Expression Levels Are Predictive of Patient Benefit (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; In a recent phase II study of onartuzumab (MetMAb), patients whose non–small cell lung cancer (NSCLC) tissue scored as positive for MET protein by immunohistochemistry (IHC) experienced a significant benefit with onartuzumab plus erlotinib (O+E) versus erlotinib. We describe development and validation of a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers as predictors of patient benefit.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Biomarkers related to MET and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative reverse transcription PCR, mutation detection techniques, and ELISA.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; A positive correlation between IHC, Western blotting, and &lt;i&gt;MET&lt;/i&gt; mRNA expression was observed in NSCLC cell lines/tissues. An IHC scoring system of MET expression taking proportional and intensity-based thresholds into consideration was applied in an analysis of the phase II study and resulted in the best differentiation of outcomes. Further analyses revealed a nonsignificant overall survival (OS) improvement with O+E in patients with high MET copy number (mean ≥5 copies/cell by FISH); however, benefit was maintained in “MET IHC-positive”/&lt;i&gt;MET&lt;/i&gt; FISH-negative patients (HR, 0.37; &lt;i&gt;P&lt;/i&gt; = 0.01). &lt;i&gt;MET&lt;/i&gt;, &lt;i&gt;EGFR&lt;/i&gt;, amphiregulin, epiregulin, or &lt;i&gt;HGF&lt;/i&gt; mRNA expression did not predict a significant benefit with onartuzumab; a nonsignificant OS improvement was observed in patients with high tumor &lt;i&gt;MET&lt;/i&gt; mRNA levels (HR, 0.59; &lt;i&gt;P&lt;/i&gt; = 0.23). Patients with low baseline plasma hepatocyte growth factor (HGF) exhibited an HR for OS of 0.519 (&lt;i&gt;P&lt;/i&gt; = 0.09) in favor of onartuzumab treatment.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; MET IHC remains the most robust predictor of OS and progression-free survival benefit from O+E relative to all examined exploratory markers. &lt;i&gt;Clin Cancer Res; 20(17); 4488–98. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Conditions for operation of semiconductor laser with negative light/current characteristic (1981)

A semiconductor laser with a controlled amount of saturable absorber states can be made to produce a negative light/current characteristic. The conditions required to achieve such a characteristic are given in the letter. Such a device can be switched on by an external light pulse when appropriately biased.
Exploring Cellular Contact Guidance Using Gradient Nanogratings (2010)

Nanoscale surface features that mimic extracellular matrix are critical environmental cues for cell contact guidance and are vital in advanced medical devices in order to manipulate cell behaviors. Among them, nanogratings (line-and-space gratings) are common platforms to study geometric effects on cell contact guidance, especially cell alignment, but generally are one pattern height per platform. In this study, we developed a strategy to fabricate controlled substrates with a wide range of pattern shapes and surface chemistries and to separate surface chemistry and topography effects. As a demonstration of this strategy, six nanograting platforms on three materials were fabricated and applied to examine and differentiate the effects of surface topography and surface chemistry on cell contact guidance of murine preosteoblasts. All of the six platforms contained the same gradient in pattern height (0 to ≈350 nm). They were prepared using nanoimprint lithography and annealing for thermoplastic materials (low molecular weight polystyrene (PS) and polymethylmethacrylate (PMMA)) and photoimprint for a thermoset material (a cross-linked dimethacrylate (DMA)). Each material contains two platforms that are only different in line-and-space pitch (420 or 800 nm). The DMA nanogratings had a reverse line-and-space profile to those of the PS and PMMA nanogratings. Using these platforms, a full range of cell alignment, from randomly orientated to completely parallel to the grating direction was achieved. Results from focal adhesion assays and scanning electronic microscopy indicated a change in cell-substrate contact from a noncomposite state (full contact) to a composite state (partial contact between cell and substrate) as pattern height increased. These gradient platforms allowed for the separation of surface chemistry and surface topography to provide insight into the mechanisms responsible for cell contact guidance on nanopatterned surfaces.
Design and In Vitro Testing of a Pressure-Sensing Syringe for Endotracheal Tube Cuffs (2012)

Endotracheal intubation is a frequently performed procedure in the prehospital setting, intensive care unit, and for patients undergoing surgery. The endotracheal tube cuff must be inflated to a pressure that prevents air leaks without compromising tracheal mucosal blood flow. For simultaneous endotracheal tube cuff inflation and measurement, we designed and tested a novel pressure-sensing syringe in vitro. The prototype was developed using a standard 10-mL polycarbonate syringe body that houses a plunger and a silicone rubber bellows, the pressure-sensing element. Bellow feasibility was determined and modeled using finite element analysis. Repeatability testing at each pressure measurement for each bellows (pressure versus deflection) was within an average standard deviation of 0.3 cm to 1.61 cm (1%-5% error). Using an aneroid manometer for comparison, there was excellent linear correlation with a Spearman rank of 0.99 (P < 0.001), up to 30 cm H(2)O.
Increasing the Structural Span of Alkyne Metathesis (2013)

A new generation of alkyne metathesis catalysts, which are distinguished by high activity and an exquisite functional group tolerance, allows the scope of this transformation to be extended beyond its traditional range. They accept substrates that were previously found problematic or unreactive, such as propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of various types, and even terminal alkynes. Moreover, post-metathetic transformations other than semi-reduction increase the structural portfolio, as witnessed by the synthesis of a annulated phenol derivative via ring-closing alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene reaction. Further examples encompass a post-metathetic transannular ketone-alkyne cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox isomerization, and a Meyer-Schuster rearrangement/oxa-Michael cascade. These reaction modes fueled model studies toward salicylate macrolides, furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A; moreover, they served as the key design elements of concise total syntheses of dehydrocurvularin (27) and the antibiotic agent A26771B (36).
Multifractal Cross-Traffic Estimation (2000)

In this paper we develop a novel model-based technique, the Delphi algorithm, for inferring the instantaneous volume of competing cross-traffic across an end-to-end path. By using only end-to-end measurements, Delphi avoids the need for data collection within the Internet. Unique to the algorithm is an efficient exponentially spaced probing packet train and a parsimonious multifractal parametric model for the cross-traffic that captures its multiscale statistical properties (including long-range dependence) and queuing behavior. The algorithm is adaptive; it requires no a priori traffic statistics and effectively tracks changes in network conditions. ns (network simulator) experiments reveal that Delphi gives accurate cross-traffic estimates for higher link utilization levels while at lower utilizations it over-estimates the cross-traffic. Also, when Delphi&amp;apos;s single bottleneck assumption does not hold it over-estimates the crosstraffic.
Assembly and Organization Processes in DNA-Directed Colloidal Crystallization* (2020)

This chapter presents an analysis of the key steps involved in the DNA-directed assembly of nanoparticles into crystallites and polycrystalline aggregates. The tailorable arrangement of nanoscale materials through directed-mechanisms has proven to be the most practical method to create ordered arrangements of nanoparticles in solution; crystalline nanoparticle aggregates have potential implications for the development of materials with unique plasmonic, photonic, electrical and magnetic properties. The chapter also presents a study of the formation process for these DNA-linked nanoparticle crystal systems, using synchrotron small angle X-ray scattering to monitor the initial formation and growth of highly-ordered 3D assemblies in 3 distinct crystal systems, showing variations in assembly parameters as a function of solution temperature, DNA length and 1- versus 2-component DNA-AuNP systems. It shows that higher temperatures are necessary for the formation of maximally ordered crystals and that increased DNA-interconnect length decreases the rate of crystal formation.
Overexpression of Vascular Endothelial Growth Factor-B in Mouse Heart Alters Cardiac Lipid Metabolism and Induces Myocardial Hypertrophy (2008)

Vascular endothelial growth factor (VEGF)-B is poorly angiogenic but prominently expressed in metabolically highly active tissues, including the heart. We produced mice expressing a cardiac-specific VEGF-B transgene via the alpha-myosin heavy chain promoter. Surprisingly, the hearts of the VEGF-B transgenic mice showed concentric cardiac hypertrophy without significant changes in heart function. The cardiac hypertrophy was attributable to an increased size of the cardiomyocytes. Blood capillary size was increased, whereas the number of blood vessels per cell nucleus remained unchanged. Despite the cardiac hypertrophy, the transgenic mice had lower heart rate and blood pressure than their littermates, and they responded similarly to angiotensin II-induced hypertension, confirming that the hypertrophy does not compromise heart function. Interestingly, the isolated transgenic hearts had less cardiomyocyte damage after ischemia. Significantly increased ceramide and decreased triglyceride levels were found in the transgenic hearts. This was associated with structural changes and eventual lysis of mitochondria, resulting in accumulation of intracellular vacuoles in cardiomyocytes and increased death of the transgenic mice, apparently because of mitochondrial lipotoxicity in the heart. These results suggest that VEGF-B regulates lipid metabolism, an unexpected function for an angiogenic growth factor.
Hypothyroidism and thyroxin substitution affect the n−3 fatty acid composition of rat liver mitochondria (1991)

The effects of hypothyroidism and of daily treatment for up to 21 days with thyroxin (T4, 0.5 micrograms/100 g body weight) on the fatty acid composition of total lipid, phosphatidylethanolamine, and phosphatidylcholine of rat liver mitochondria were studied. The fatty acid compositions of hypothyroid and euthyroid (control) rats of similar age were compared. The n-6 and n-3 polyunsaturated fatty acids (PUFA) were affected differently by the hypothyroid state. The levels of linoleic (18:2n-6), gamma-linolenic (18:3n-6) and dihomo-gamma-linolenic acids (20:3n-6) were higher in hypothyroid rats than in controls, while the level of arachidonic acid (20:4n-6) was lower, which suggests an impairment of the elongase and desaturase activities. The n-3 polyunsaturated fatty acids, eicosapentaenoic (EPA, 20:5n-3) and docosapentaenoic (22:5n-3) acids, were higher in hypothyroid rats, whereas the linolenic acid (18:3n-3) content remained constant. The level of docosahexaenoic acid (DHA, 22:6n-3) was dramatically decreased in hypothyroid rats, while the levels of C22 n-6 fatty acids were unchanged. The differences were probably due to the competition between n-3 and n-6 PUFA for desaturases, elongases and acyltransferases. When hypothyroid rats were treated with thyroxin, the changes induced by hypothyroidism in the proportions of n-6 fatty acids were rapidly reversed, while the changes in the n-3 fatty acids were only partially reversed. After 21 days of thyroxin treatments, the DHA content was only half as high in hypothyroid rats than in euthyroid rats. These results suggest that the conversion of 18:2n-6 to 20:4n-6 is suppressed in the hypothyroid state which favors the transformation of 18:3n-3 to 20:5n-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery (2018)

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and three maternally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins. We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such as mRNA export, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in humans.
Optical Performance Monitoring (2004)

Progress in optical networking has stimulated interest in optical performance monitoring (OPM), particularly regarding signal quality measures such as optical signal-to-noise ratio (SNR), Q-factor, and dispersion. These advanced monitoring methods have the potential to extend fault management and quality-of-service (QoS) monitoring into the optical domain. This paper reviews OPM applications and techniques, while examining the role of OPM as an enabling technology for advances in high-speed and optically switched networks.
High-temperature Oxidation of Carborane-Siloxane-Acetylene-based Polymer (1996)

A processable new thermosetting polymer containing carborane and siloxane groups with acetylenic linkages was examined for antioxidative properties during high-temperature oxygen exposure. Samples of the polymer were annealed in argon or air at 320–400°C or argon at 900°C and oxidized at 400 and 500°C. Their structure and composition were analyzed by scanning electron microscopy, x-ray photoelectron spectroscopy, scanning Auger microprobe scattering and Raman microprobe scattering. Samples heated to 400°C in argon exhibited little or no inorganic segregation, but developed surface layers of boron and silicon oxide when heated to 400°C in air. Samples annealed in argon to 900°C and then oxidized at 500°C for up to 100 h developed a continuous silicon oxide surface layer with almost no underlying boron oxide. The layer retarded oxidation of the sample bulk at 500°C.
A dual image processing pipeline camera with CE applications (2011)

The implementation of a dual image processing pipeline camera on a state-of-art FPGA system is described. This camera can simultaneously acquire dual images of a scene and process, analyze and merge both images to enable a range of realtime image enhancement algorithms to be explored. Several examples of image enhancement algorithms implemented on the prototype camera are described.
Stereospecificity of Ketoreductase Domains 1 and 2 of the Tylactone Modular Polyketide Synthase (2008)

Tylactone synthase (TYLS) is a modular polyketide synthase that catalyzes the formation of tylactone (1), the parent aglycone precursor of the macrolide antibiotic tylosin. TYLS modules 1 and 2 are responsible for the generation of antidiketide and triketide intermediates, respectively, each bound to an acyl carrier protein (ACP) domain. Each module harbors a ketoreductase (KR) domain. The stereospecificity of TYLS KR1 and TYLS KR2 has been determined by incubating each of the recombinant ketoreductase domains with reconstituted ketosynthase-acyltransferase [KS][AT] and ACP domains from the 6-deoxyerythronolide B synthase (DEBS) in the presence of the N-acetylcysteamine thioester of syn-(2S,3R)-2-methyl-3-hydroxypentanoate (6), methylmalonyl-CoA, and NADPH resulting in the exclusive formation of the ACP-bound (2R,3R,4S,5R)-2,4-methyl-3,5-dihydroxyhepanoyl triketide, as established by GC-MS analysis of the TMS ether of the derived triketide lactone 7. Both TYLS KR1 and KR2 therefore catalyze the stereospecific reduction of the 2-methyl-3-ketoacyl-ACP substrate from the re-face, with specificity for the reduction of the (2R)-methyl (D) diastereomer. The dehydration that is catalyzed by the dehydratase (DH) domains of TYLS module 2 to give the unsaturated (2E,4S,5R)-2,4-dimethyl-5-hydroxyhept-2-enoyl-ACP2 is therefore a syn elimination of water.
Living Carbocationic Polymerization. VII. Living Polymerization of Isobutylene by Tertiary Alkyl (or Aryl) Methyl Ether/Boron Trichloride Complexes (1987)

Abstract It has been discovered that the living polymerization of isobutylene (IB) can be induced by MeORt/BCl3 initiating systems in CH2C12or CH3C1 at −10 and −30°C. Diagnostic proof for the living polymerizations are 1) proportionality of M n to polyisobutylene (PIB) formed and 2) independence of number of PIB chains of amount of PIB formed. By the use of agedC(CH3)3CH2OMe/BCl3 and C6H5C(CH3)2OMe/BCl3 systems, initiation efficiency (leff) ≍ 100% and M n is determined by the [monomer]0/[initiator]0 ratio. Polymerizations quenched by methanol yielded f-chloro end groups.
Vascular Access: Comparison of US Guidance with the Sonic Flashlight and Conventional US in Phantoms (2006)

Learning and performance of vascular access were significantly faster with the sonic flashlight than with conventional US, and vascular access could be gained in a cadaver; the sonic flashlight is ready for clinical trials.
Spatial epigenome–transcriptome co-profiling of mammalian tissues (2023)

Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context<sup>1-5</sup>. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution. These were applied to embryonic and juvenile mouse brain, as well as adult human brain, to map how epigenetic mechanisms control transcriptional phenotype and cell dynamics in tissue. Although highly concordant tissue features were identified by either spatial epigenome or spatial transcriptome we also observed distinct patterns, suggesting their differential roles in defining cell states. Linking epigenome to transcriptome pixel by pixel allows the uncovering of new insights in spatial epigenetic priming, differentiation and gene regulation within the tissue architecture. These technologies are of great interest in life science and biomedical research.
The KDD 2022 Workshop on Causal Discovery (CD2022) (2022)

Causal relationships have been utilized in almost all disciplines, and the research into causal discovery has attracted a lot of attention in the last few years. Traditionally, causal relationships are identified by making use of interventions or randomized controlled experiments. However, conducting such experiments is often expensive or even impossible due to cost or ethical concerns. Therefore, there has been an increasing interest in discovering causal relationships based on observational data, and in the past few decades, significant contributions have been made to this field by computer scientists.
Evaluation of the NKD-1 mutation in carcinoma of the uterine endometrium. (2010)

e15537 Background: Misregulation of the WNT/β-catenin pathway is characteristic of some cancers, most notably colorectal and endometrial cancer. For example, mutations in the CTNNB1 gene occur in at least 15% of endometrial cancers. However, stabilization of the β-catenin protein occurs more frequently in endometrial cancers (∼40% of cases) suggesting that mutations in other WNT pathway components may lead to misregulation of this pathway in endometrial cancer. Naked cuticle (NKD) proteins inhibit WNT signaling, and hence, alteration of NKD gene activity in mammals might activate WNT. A recent study showed that NKD1 exon 10 mutations were frequent in colorectal cancers (primary tumors and cell lines) that did not harbor mutations in other WNT/β-catenin pathway components, raising the question as to whether mutations in NKD1 gene might also be significant in endometrial carcinogenesis. We thus sought to evaluate whether NKD1 mutations also characterize endometrial adenocarcinoma. Methods: Genomic DNA was extracted from 3 endometrial cancer cell lines and 53 primary endometrial tumor samples from patients at UT Southwestern hospitals. Exon 10 of the NKD1 gene was subjected to bidirectional PCR sequencing. Automated base calls generated by sequence analysis software were visually inspected to confirm accurate variant detection. Results: Of the 53 endometrial tumor samples evaluated, 29 were endometrioid, 10 carcinosarcoma, 3 clear cell, 4 mixed, and 7 were of unclassified histology. No NKD1 mutations including single base insertions or deletions of the exon-10 poly-(C)7 tract were identified that would result in the synthesis of truncated NKD1 protein, as has been shown to occur in colorectal adenocarcinomas. Conclusions: No NKD1 gene mutations were found in any uterine cancers, arguing that other defects in this pathway account for the frequent stabilization of β-catenin. No significant financial relationships to disclose.
Shining a Light on Human Pose: On Shadows, Shading and the Estimation of Pose and Shape (2007)

Strong lighting is common in natural scenes yet is often viewed as a nuisance for object pose estimation and tracking. In human shape and pose estimation, cast shadows can be confused with foreground structure while self shadowing and shading variation on the body cause the appearance of the person to change with pose. Rather than attempt to minimize the effects of lighting and shadows, we show that strong lighting in a scene actually makes pose and shape estimation more robust. Additionally, by recovering multiple body poses we are able to automatically estimate the lighting in the scene and the albedo of the body. Our approach makes use of a detailed 3D body model, the parameters of which are directly recovered from image data. We provide a thorough exploration of human pose estimation under strong lighting conditions and show: 1. the estimation of the light source from cast shadows; 2. the estimation of the light source and the albedo of the body from multiple body poses; 3. that a point light and cast shadows on the ground plane can be treated as an additional "shadow camera" that improves pose and shape recovery, particularly in monocular scenes. Additionally we introduce the notion of albedo constancy which employs lighting normalized image data for matching. Our experiments with multiple subjects show that rather than causing problems, strong lighting improves human pose and shape estimation.