gebhart/patrepeval huggingface dataset:
CONTINUOUS SYSTEMIC SECRETION OF A LYSOSOMAL ENZYME BY GENETICALLY MODIFIED MOUSE SKIN FIBROBLASTS (1993)

Lysosomal enzymes secreted or externally supplied into the extracellular medium can be internalized by cells and targeted to lysosomes after binding to specific membrane receptors. This process allows for the replacement of the missing enzyme activity in deficient cells. Using a retroviral vector, we have introduced the human beta-glucuronidase cDNA into primary mouse skin fibroblasts. The genetically modified cells were then engrafted into neo-organs that had been previously implanted into the peritoneal cavity of syngeneic recipient mice. The hypervascularized structures, made of collagen and basic fibroblast growth factor-coated synthetic fibers embedded into extracellular matrix gel, allowed in vivo survival of engrafted fibroblasts that expressed the human beta-glucuronidase cDNA for at least 3 months. The human enzyme was detected in the liver, lung, and spleen of experimental animals, but became undetectable after removal of the neo-organ. This observation indicated that the human enzyme was secreted into the serum and then captured by distant organs. The use of genetically modified fibroblasts implanted into neo-organs may, therefore, represent a convenient approach to enzyme replacement therapy in lysosomal storage diseases.
Experimental infection and co-infection of dogs with Anaplasma platys and Ehrlichia canis: hematologic, serologic and molecular findings (2010)

The results of this study demonstrate that simultaneous or sequential infection with A. platys and E. canis can alter various pathophysiological parameters in experimentally infected dogs, and because natural exposure to multiple tick-borne pathogens occurs frequently in dogs, awareness of co-infection is important in clinical practice.
The Total Synthesis of Heliquinomycinone (2001)

A strategy for the synthesis of heliquinomycin, a selective helicase inhibitor, hinges on the spirocyclization of precursor 3. Naphthofuran 1 and aldehyde 2 were readily prepared and used in the synthesis of 3. The key steps in the total synthesis of heliquinomycinone (4) include the regioselective dihydroxylation of 3, and a novel spirocyclization under Mitsunobu conditions.
High-grade serous ovarian and peritoneal cancers display distinct genetic and post-translational signatures – a criterion to treat them differently? (2016)

Introduction and aim: High-grade serous ovarian (HGSOC), tubal, and peritoneal adenocarcinomas (HGSPC), commonly presenting at an advanced stage and being associated with high mortality rates, are currently treated the same way. We hypothesize that HGSOC and HGSPC are distinguishable by their genetic and molecular profiles and hence are different diseases.\n\nMaterial and methods: Two independent cohorts (560 patients) were reviewed regarding relapse- and disease-free survival in HGSOC and HGSPC; differential gene expression was determined by Tothill data analysis; differential glycoprotein and post-translational glycan signatures were determined in cancer tissues (mass spectrometry) and in blood plasma (printed glycan array).\n\nResults: HGSPC patients relapse and decease earlier than HGSOC patients, indicating that HGSPC is more aggressive. HGSPC and HGSOC are distinguishable with high discriminatory power (1) on the gene expression level, with alcohol dehydrogenase 1B (ADH1B) being to top single-gene discriminator, and even better with a set of 40 differentially expressed genes; (2) on the level of blood-derived anti-glycan antibodies against specific glycans printed on the array; and (3) on the basis of distinct profiles of N- and O-glycans attached to glycoproteins of cancer cells. In the latter context, unique N-linked structure LacdiNAc on glycoproteins was detected preferentially in HGSOC tissues.\n\nConclusion: HGSOC and HGSPC cells display distinct molecular signatures on the genetic, post-translational, and anti-glycan antibody levels, and therefore should be considered two different diseases and treated individually according to their profiles. The distinction by the antibodies may serve diagnostic purposes and the LacdiNAc-structure as ideal candidate for targeted HGSOC therapies.
Time-domain diffuse optical tomography processing by using the Mellin–Laplace transform (2012)

We investigate the use of the Mellin-Laplace transform for reconstructing optical parameters from time-resolved optical tomography in diffusive media. We present here its definition, its mathematical properties, and its sensitivity to variations of optical properties. The method was validated on two-dimensional reconstructions from simulation in the reflection geometry. We conclude that reconstructions based on the Mellin-Laplace transform are more robust to noise than the methods using first moments.
Time Aura (2001)

Historically one of the visions for human-computer symbiosis has been to augment human intelligence and extend people's cognitive abilities. In this paper, we present two visually-based systems to enhance a person's ability to flexibly control their pace while engaged in a cognitively demanding activity. In these investigations, we explore pacing interfaces that minimize the cognitive demands for assessing a current pace, provide ambient cues that can be quickly interpreted without incurring significant interruption from the current task, and place knowledge in the world to flexibly support different pacing strategies. Evaluation of our pacing interfaces shows that technology can successfully support pacing.
Data from A &lt;i&gt;let-7&lt;/i&gt; microRNA-Binding Site Polymorphism in &lt;i&gt;KRAS&lt;/i&gt; Predicts Improved Outcome in Patients with Metastatic Colorectal Cancer Treated with Salvage Cetuximab/Panitumumab Monotherapy (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; An inherited mutation in &lt;i&gt;KRAS&lt;/i&gt; (LCS6-variant or rs61764370) results in altered control of the &lt;i&gt;KRAS&lt;/i&gt; oncogene. We studied this biomarker's correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with metastatic colorectal cancer.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; LCS6-variant and &lt;i&gt;KRAS/BRAF&lt;/i&gt; mutational status was determined in 512 patients with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-variant allele to therapy exposure.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; In this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-variant (TG/GG), which was found twice as frequently in the &lt;i&gt;BRAF&lt;/i&gt;-mutated versus the wild-type (WT) group (&lt;i&gt;P&lt;/i&gt; = 0.03). LCS6-variant patients had significantly longer progression- free survival (PFS) with anti-EGFR mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; &lt;i&gt;P&lt;/i&gt; = 0.019) and in the double WT (&lt;i&gt;KRAS&lt;/i&gt; and &lt;i&gt;BRAF&lt;/i&gt;) patient population (18 vs. 10.4 weeks; &lt;i&gt;P&lt;/i&gt; = 0.039). Combination therapy (mAbs plus chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; LCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm the importance of this mutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation. &lt;i&gt;Clin Cancer Res; 20(17); 4499–510. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Tracking using self-initialising Active Meshes (1999)

This paper describes a method of visual tracking using an 'active-mesh' that is automatically created and configured directly from a single frame of an image sequence. The aim of this approach is to perform visual tracking in unconstrained motion environments, allowing movement of the camera, the scene and even the inclusion of background-independent moving objects.
Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer (2020)

Genome wide association studies (GWAS) and large scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ~14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS comprising of 15,748 breast cancer cases and 18,084 controls, and 46,785 cases and 42,892 controls from 41 studies genotyped on a 200K custom array (iCOGS). Analyses were restricted to women of European ancestry. Genotypes for more than 11M SNPs were generated by imputation using the 1000 Genomes Project reference panel. We identified 15 novel loci associated with breast cancer at P<5×10−8. Combining association analysis with ChIP-Seq data in mammary cell lines and ChIA-PET chromatin interaction data in ENCODE, we identified likely target genes in two regions: SETBP1 on 18q12.3 and RNF115 and PDZK1 on 1q21.1. One association appears to be driven by an amino-acid substitution in EXO1.
van der Waals interaction at a material wedge (1989)

The problem of evaluating the van der Waals attraction energy of an atom or microparticle adsorbed near the edge of a straight material wedge of arbitrary opening angle is considered. In order to disentangle more clearly the effect of the wedge geometry from the material parameters, a simple model is used in which the particle is represented by a harmonic oscillator and the substrate by a perfect conductor. By a straightforward extension of the method of images of classical electrostatics, the dipolar coupling of the particle to the substrate is constructed from which new oscillator frequencies can be determined as a function of its position relative to the edge and of the wedge angle. The van der Waals energy is given by the shift in zero-point energy of the oscillator coupled to itself via its images. For a physisorbed atom crossing the edge of a wedge material, the detailed shape of the van der Waals energy barrier (respectively, well) offered by a convex (respectively, concave) wedge is displayed and compared with approximate results deduced from a pairwise summation of Lennard-Jones interactions. The interest of these results for the dynamics and kinetics of sorption by microporous solids is briefly discussed.
SERS intensity optimization by controlling the size and shape of faceted gold nanoparticles (2007)

Abstract In this work, we experimentally investigated the surface‐enhanced Raman spectroscopy (SERS) activity of faceted gold nanoparticles, which have been theoretically predicted to yield giant enhancements. Glycine was used to determine the SERS activity as a function of pH and ionic strength and to estimate the corresponding enhancement factor (EF). By optimizing the synthesis conditions of the flat prismatic nanoparticles, it was possible to control their size and shape. We demonstrate that the maximum SERS intensity increases with the edge length of the triangle, reaching a maximum EF of ∼10 13 for 1.9 µm triangles (the largest tested). The corresponding glycine detection limit was as low as 10 −12 M , close to the single‐molecule threshold. Copyright © 2007 John Wiley &amp; Sons, Ltd.
Search Efficiency for Tactile Features Rendered by Surface Haptic Displays (2014)

Haptic interfaces controlled by a single fingertip or hand-held probe tend to display surface features individually, requiring serial search for multiple features. Novel surface haptic devices, however, have the potential to provide displays to multiple fingertips simultaneously, affording the possibility of parallel search. Using variable-friction surface haptic devices, we investigated the ability of participants to detect a target feature among a set of distractors in parallel across the fingers. We found that searches for a material property (slipperiness) and an illusory shape (virtual hole) were significantly impaired by distractors, while search for an abrupt discontinuity (virtual edge) was not. The efficiency of search for edges rendered by surface haptics suggests that they engage primitive detectors in the haptic perceptual system.
Model-guided Examination of Human Signatures Produced by an Array-based Radar System (2009)

Abstract : We adapt X-patch models and processing to produce moving target indication (MTI) signatures that better represent those produced by an array-based system. We then consider the resulting data as a function of both depression angle and azimuth (or viewing) angle.
Dyspnoe-Algorithmen für Praxis und Notfallstation (2009)

The evaluation of dyspnea in the Emergency Department (ED) is a critical step in the diagnostic procedure, especially when cardiopulmonary disease is suspected. Because dyspnea is a symptom in which many different afferent mechanisms are involved, a large number of underlying causes must be considered, alone or in combination. Qualitative and quantitative aspects of difficult or laboured breathing may vary extremely between patients. Therefore, especially under time pressure in emergency situations, it is important to consider a very broad differential diagnosis, and at the same time use a standardized protocol or diagnostic algorithms for the initial work-up.In this article, a standardized work-up published by family practitioners is compared to a standardized work-up proposed by our ED. While practitioners may safely use a multi-step algorithmic approach, it is important in the ED to consider all possible serious underlying conditions at the same time. Over 90 % of all emergency situations are accounted for by only 7 different disease groups. Therefore, all of these must be considered simultaneously in a protocol that is useful for emergency physicians.
Storage of sparse files using parallel log-structured file system (2023)

A sparse file is stored without holes by storing a data portion of the sparse file using a parallel log-structured file system; and generating an index entry for the data portion, the index entry comprising a logical offset, physical offset and length of the data portion. The holes can be restored to the sparse file upon a reading of the sparse file. The data portion can be stored at a logical end of the sparse file. Additional storage efficiency can optionally be achieved by (i) detecting a write pattern for a plurality of the data portions and generating a single patterned index entry for the plurality of the patterned data portions; and/or (ii) storing the patterned index entries for a plurality of the sparse files in a single directory, wherein each entry in the single directory comprises an identifier of a corresponding sparse file.
Human glia can both induce and rescue aspects of disease phenotype in Huntington disease (2016)

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.
Checkpoint Inhibition in Bladder Cancer: Clinical Expectations, Current Evidence, and Proposal of Future Strategies Based on a Tumor-Specific Immunobiological Approach (2021)

In contrast with other strategies, immunotherapy is the only treatment aimed at empowering the immune system to increase the response against tumor growth. Immunotherapy has a role in the treatment of bladder cancer (BC) due to these tumors' high tumor mutational burden (TMB) and mostly prominent immune infiltrate. The therapy or combination has to be adjusted to the tumor's immunobiology. Recently, a new class of immunotherapeutic agents, immune checkpoint inhibitors (ICI), has shown potential in increasing treatment chances for patients with genitourinary cancers, improving their oncological outcomes. The clinical efficacy of ICI has been shown in both the first-line treatment of cisplatin-ineligible patients, with programmed death ligand 1 (PD-L1)-positive tumors (atezolizumab, pembrolizumab), and in second-line settings, for progression after platinum-based chemotherapy (atezolizumab, pembrolizumab, and nivolumab for FDA and EMA; durvalumab and avelumab for FDA alone). Predicting the response to ICI is important since only a subset of patients undergoing ICI therapy develop a concrete and lasting response. Most of the patients require a different therapy or therapy combination to achieve tumor control. The cancer immunity cycle provides a conceptual framework to assist therapy selection. Biomarkers to predict response to ICI must identify where the cancer immunity cycle is disrupted. We reviewed the current knowledge on ICI treatment in BC, going from basic science to current data and available clinical evidence. Secondly, a critical analysis of published data is provided, and an original panel of biomarkers able to predict response to ICI treatment, based on tumor-specific immune profiling, is proposed.
Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer (2015)

The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites.
Exploitation of Lipid Components by Viral and Host Proteins for Hepatitis C Virus Infection (2012)

Hepatitis C virus (HCV), which is a major causative agent of blood-borne hepatitis, has chronically infected about 170 million individuals worldwide and leads to chronic infection, resulting in development of steatosis, cirrhosis, and eventually hepatocellular carcinoma. Hepatocellular carcinoma associated with HCV infection is not only caused by chronic inflammation, but also by the biological activity of HCV proteins. HCV core protein is known as a main component of the viral nucleocapsid. It cooperates with host factors and possesses biological activity causing lipid alteration, oxidative stress, and progression of cell growth, while other viral proteins also interact with host proteins including molecular chaperones, membrane-anchoring proteins, and enzymes associated with lipid metabolism to maintain the efficiency of viral replication and production. HCV core protein is localized on the surface of lipid droplets in infected cells. However, the role of lipid droplets in HCV infection has not yet been elucidated. Several groups recently reported that other viral proteins also support viral infection by regulation of lipid droplets and core localization in infected cells. Furthermore, lipid components are required for modification of host factors and the intracellular membrane to maintain or up-regulate viral replication. In this review, we summarize the current status of knowledge regarding the exploitation of lipid components by viral and host proteins in HCV infection.
Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells (2016)

Chemotaxis, the directional migration of cells in a chemical gradient, is robust to fluctuations associated with low chemical concentrations and dynamically changing gradients as well as high saturating chemical concentrations. Although a number of reports have identified cellular behavior consistent with a directional memory that could account for behavior in these complex environments, the quantitative and molecular details of such a memory process remain unknown. Using microfluidics to confine cellular motion to a 1D channel and control chemoattractant exposure, we observed directional memory in chemotactic neutrophil-like cells. We modeled this directional memory as a long-lived intracellular asymmetry that decays slower than observed membrane phospholipid signaling. Measurements of intracellular dynamics revealed that moesin at the cell rear is a long-lived element that when inhibited, results in a reduction of memory. Inhibition of ROCK (Rho-associated protein kinase), downstream of RhoA (Ras homolog gene family, member A), stabilized moesin and directional memory while depolymerization of microtubules (MTs) disoriented moesin deposition and also reduced directional memory. Our study reveals that long-lived polarized cytoskeletal structures, specifically moesin, actomyosin, and MTs, provide a directional memory in neutrophil-like cells even as they respond on short time scales to external chemical cues.
Preliminary Report: Effect of Encainide and Flecainide on Mortality in a Randomized Trial of Arrhythmia Suppression after Myocardial Infarction (1989)

The occurrence of ventricular premature depolarizations in survivors of myocardial infarction is a risk factor for subsequent sudden death, but whether antiarrhythmic therapy reduces the risk is not known. The Cardiac Arrhythmia Suppression Trial (CAST) is evaluating the effect of antiarrhythmic therapy (encainide, flecainide, or moricizine) in patients with asymptomatic or mildly symptomatic ventricular arrhythmia (six or more ventricular premature beats per hour) after myocardial infarction. As of March 30, 1989, 2309 patients had been recruited for the initial drug-titration phase of the study: 1727 (75 percent) had initial suppression of their arrhythmia (as assessed by Holter recording) through the use of one of the three study drugs and had been randomly assigned to receive active drug or placebo. During an average of 10 months of follow-up, the patients treated with active drug had a higher rate of death from arrhythmia than the patients assigned to placebo. Encainide and flecainide accounted for the excess of deaths from arrhythmia and nonfatal cardiac arrests (33 of 730 patients taking encainide or flecainide [4.5 percent]; 9 of 725 taking placebo [1.2 percent]; relative risk, 3.6; 95 percent confidence interval, 1.7 to 8.5). They also accounted for the higher total mortality (56 of 730 [7.7 percent] and 22 of 725 [3.0 percent], respectively; relative risk, 2.5; 95 percent confidence interval, 1.6 to 4.5). Because of these results, the part of the trial involving encainide and flecainide has been discontinued. We conclude that neither encainide nor flecainide should be used in the treatment of patients with asymptomatic or minimally symptomatic ventricular arrhythmia after myocardial infarction, even though these drugs may be effective initially in suppressing ventricular arrhythmia. Whether these results apply to other patients who might be candidates for antiarrhythmic therapy is unknown.