gebhart/patrepeval huggingface dataset:
Mutations by Next Generation Sequencing in Stool DNA from Colorectal Carcinoma Patients - A Literature Review and our Experience with this Methodology (2016)

It is well-known that colorectal carcinoma is a disease involving multistep carcinogenesis (hyperplasia-adenoma-carcinoma-metastasizing carcinoma). It is also a disease where therapeutically important driver mutations (especially in the EGFR signaling pathway) have been identified. Since genetic mutations can serve as good diagnostic and predictive markers, their reliable detection in the early stages of the disease and also in the follow-up of treatment efficacy is crucial. There is a fundamental problem encountered with the commonly used formalin-fixed paraffin-embedded (FFPE) specimens from biopsied tumor tissue i.e. it is unlikely that the material for the mutation analysis will be available in either the early stage of the disease or during the treatment period. Therefore recently attempts have been made to identify reliable markers from plasma/serum or from stool specimens. In particular, non-invasive stool specimens have been speculated to represent the situation of ongoing tumorigenesis and thus they can be used to assess treatment efficacy in the follow-upof the patient. The key aims of this paper are firstly, to review the key methodological points when studying genomic alterations in DNA extracted from cells in stool specimens, and secondly, to review results related to biomarker screening and their therapeutic importance. A further aim is to present our new findings by focusing on the issues inherent in Next Generation Sequencing of stool specimens from patients with gastrointestinal tumors. Even though the focus of our paper is human genomic alterations in stool specimens, in our future aspects chapter, we also deal with the bacterial spectrum and its possible interaction with the genomic mutations.
211. Proteomic identification of caldesmon as one of the physiological substrates of proprotein convertase 6 during decidualisation (2008)

We have previously demonstrated that proprotein convertase 5/6 (PC6), a member of the proprotein convertase (PC) family, is a critical endometrial factor for implantation. PC6 is upregulated in the endometrium specifically at implantation in association with epithelial differentiation (in human and monkey) and stromal cell decidualisation (in the mouse, human and monkey). Knockdown of endometrial PC6 during early pregnancy in mice in vivo led to complete failure of implantation, while blocking of PC6 production in human endometrial stromal cells in vitro inhibited decidualisation. PCs convert a range of precursor proteins of important functions into their bioactive forms; they are thus regarded as critical ‘master switch’ molecules. We hypothesise that PC6 exerts its roles in the endometrium by regulating proteins of diverse functions essential for implantation. In this study, we utilised proteomic technology and aimed to identify proteins that are specifically cleaved by PC6 in human endometrial stromal cells (HESC) during decidualisation. HESC were decidualised with cyclic AMP, the cell lysates were treated with and without recombinant human PC6-A (rPC6-A), and the 2D Differential in Gel Electrophoresis (2D DiGE) protein profiles were compared between the two treatments. We identified several proteins which were differentially cleaved following the addition of rPC6-A. Mass spectrometric analysis confirmed that the most abundant of these were caldesmon, tropomyosin-2, tropomyosin-4, hypoxia Inducible factor-1 and chloride intracellular channel-1. These proteins showed spot shifts in hPC6-A treated HESC lysates consistent with hPC6-A cleavage. western blot analysis confirmed the specific cleavage of caldesmon by PC6 in HESCs, and immunohistochemical analysis showed co-localisation of caldesmon and PC6 in decidual cells in human endometrial tissue. Given that caldesmon is a structural protein previously found to be involved in actin filament reorganisation, our results strongly suggest that PC6 is a mediator of structural remodelling of stromal cells during decidualisation in the endometrium.
Rare-earth elements in synthetic zircon: Part 2. A single-crystal X-ray study of xenotime substitution (2001)

Zircon crystals synthesized in a Li-Mo oxide melt and doped with trivalent lanthanides and Y (REE), both with and without P, were examined by single-crystal X-ray diffraction (XRD). REE are incorporated into the Zr site in the zircon structure, and some Zr appears to be displaced to the Si site. Crystals doped with middle REE (MREE, Sm to Dy) and Y, plus P follow the xenotime substitution (REE3+ + P5+ = Zr4+ + Si4+) rather closely, whereas crystals doped with heavy REE (HREE, Er to Lu) deviate from the xenotime substitution, having REE:P atomic ratios significantly greater than one. Xenotime substitution requires that P5+ replace Si4+, but this substitution becomes limited by strain at the Si site in HREE-doped crystals. As Si sites become saturated with P5+, additional charge balance in synthetic zircon crystals may be provided by Mo6+ and Li+ from the flux entering interstitial sites, accounting for an additional 0.3 to 0.6 at% HREE beyond that balanced by P5+ ions. Heavy REE are more compatible in the zircon structure than are LREE and MREE, and HREE substitution is ultimately limited by the inability of the zircon structure to further accommodate charge-compensating elements. Thus the limit on REE concentrations in zircon is not a simple function of REE3+ ionic radii but depends in a complex way on structural strain at Zr and Si sites, which act together to limit REE and P incorporation. The mechanisms that limit the coupled xenotime substitution change from LREE to HREE. This change means that REE fractionation in zircon may vary according to the availability of charge-compensating elements. REE partition coefficients between zircon and melt must also depend in part on the availability of charge-compensating elements and their compatibility in the zircon structure.
Data from Intratumoral Resolution of Driver Gene Mutation Heterogeneity in Renal Cancer Using Deep Learning (2023)

&lt;div&gt;Abstract&lt;p&gt;Intratumoral heterogeneity arising from tumor evolution poses significant challenges biologically and clinically. Dissecting this complexity may benefit from deep learning (DL) algorithms, which can infer molecular features from ubiquitous hematoxylin and eosin (H&amp;E)–stained tissue sections. Although DL algorithms have been developed to predict some driver mutations from H&amp;E images, the ability of these DL algorithms to resolve intratumoral mutation heterogeneity at subclonal spatial resolution is unexplored. Here, we apply DL to a paradigm of intratumoral heterogeneity, clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer. Matched IHC and H&amp;E images were leveraged to develop DL models for predicting intratumoral genetic heterogeneity of the three most frequently mutated ccRCC genes, &lt;i&gt;BAP1, PBRM1&lt;/i&gt;, and &lt;i&gt;SETD2&lt;/i&gt;. DL models were generated on a large cohort (&lt;i&gt;N&lt;/i&gt; = 1,282) and tested on several independent cohorts, including a TCGA cohort (&lt;i&gt;N&lt;/i&gt; = 363 patients) and two tissue microarray (TMA) cohorts (&lt;i&gt;N&lt;/i&gt; = 118 and 365 patients). These models were also expanded to a patient-derived xenograft (PDX) TMA, affording analysis of homotopic and heterotopic interactions of tumor and stroma. The status of all three genes could be inferred by DL, with &lt;i&gt;BAP1&lt;/i&gt; showing the highest sensitivity and performance within and across tissue samples (AUC = 0.87–0.89 on holdout). &lt;i&gt;BAP1&lt;/i&gt; results were validated on independent human (AUC = 0.77–0.84) and PDX (AUC = 0.80) cohorts. Finally, &lt;i&gt;BAP1&lt;/i&gt; predictions correlated with clinical outputs such as disease-specific survival. Overall, these data show that DL models can resolve intratumoral heterogeneity in cancer with potential diagnostic, prognostic, and biological implications.&lt;/p&gt;Significance:&lt;p&gt;This work demonstrates the potential for deep learning analysis of histopathologic images to serve as a fast, low-cost method to assess genetic intratumoral heterogeneity.&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/cancerres/article/doi/10.1158/0008-5472.CAN-22-2040" target="_blank"&gt;See related commentary by Song et al., p. 2672&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
p53 mediates density‐dependent growth arrest (2004)

While the stress-response-associated importance of the p53 tumor suppressor is well established, recent studies have also linked p53 with several basic parameters in the normal behavior of cells. Here, we present evidence that basal p53 expression in WI38 human embryonic lung fibroblasts restricts growth rate and mediates density-dependent inhibition of growth and the associated G1 phase arrest of the cell cycle by affecting the density-dependent regulation of p16/INK4a. Additionally, we show that prolonged culturing of hTert-immortalized WI38 cells leads to a loss of density-dependent growth inhibition that correlates with p27/KIP deregulation as well as the previously shown INK4a locus silencing, and to an onset of contact-induced, p53-dependent cell death.
Strain differences in cuprizone induced demyelination (2017)

These observations suggest that CD1 mice are less vulnerable to cuprizone-induced demyelination than C57BL/6 mice and thus genetic background factors appear to influence the susceptibility to cuprizone-induced demyelination.
Glucagonlike peptide 1 (1997)

Glucagonlike peptide 1 is a gut hormone with multiple functions. In addition to (glucose-dependently) stimulating insulin and inhibiting glucagon secretion, it decelerates gastric emptying and enhances (pro)insulin biosynthesis. In addition to these well-established actions, recent studies suggest an important role in the central regulation of food and water intake and possibly as a minor stimulus to thyrotropin secretion. Further effects on “peripheral” tissues involved in the regulation of carbohydrate metabolism (liver, muscle, and adipose tissue) are debated but probably make only minor contributions on the level of the whole organism. The well-preserved activity of glucagonlike peptide 1 in type 2 diabetes has led to the suggestion that this hormone or its analogues may be used as new therapeutic agents to reduce or even normalize hyperglycemia in patients with non-insulin dependent diabetes. Reductions in glucagon plasma levels and motility effects are also observed in patients with type 1 diabetes, leading to a significant reduction in fasting and postprandial glycemia. A clinically useful preparation of glucagonlike peptide 1, however, has yet to be developed.
Pneumococcal empyema and complicated pneumonias: global trends in incidence, prevalence, and serotype epidemiology (2014)

This review evaluates the serotype epidemiology of complicated pneumococcal pneumonia (CPP) during the period 1990-2012. PubMed and EMBASE were searched using the terms "empyema", "complicated pneumonia", "pleural infection", "necrotizing pneumonia", "pleural effusion", "parapneumonic effusion", "pneumatocele", or "lung abscess"; "pneumococcal" or "Streptococcus pneumoniae"; and "serotype" for studies on the epidemiology of complicated pneumonias published from January 1, 1990 to October 1, 2013. Studies with data on incidence and serotypes were included; reviews, case reports, and conference abstracts were excluded. Of 152 papers, 84 fitted the inclusion criteria. A few pneumococcal serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14, and 7F. CPP was a more common manifestation of pneumococcal disease among older (>2 years old) than younger children. The data support increases in both reported incidence rates and proportions of CPP in children and adults during the period 1990-2012; specific increases varied by geographic region. The proportions of serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas most studies show declines in serotype 14. Serotype 1 has been a predominant cause of CPP since 1990, while antibiotic resistance was infrequent among serotype 1 isolates. The reported incidence and proportions of CPP among pneumonia cases steadily increased from 1990 to 2012. Several factors might account for these increases, including enhanced disease detection due to a higher index of suspicion, more sophisticated diagnostic assays, and changes in the prevalence of serotypes with capacity to invade the pleural space that were not targeted by the 7-valent pneumococcal conjugate vaccine (PCV7).
Elucidating collective translocation of nanoparticles across the skin lipid matrix: a molecular dynamics study (2023)

The top layer of skin, the stratum corneum, provides a formidable barrier to the skin. Nanoparticles are utilized and further explored for personal and health care applications related to the skin. In the past few years, several researchers have studied the translocation and permeation of nanoparticles of various shapes, sizes, and surface chemistry through cell membranes. Most of these studies focused on a single nanoparticle and a simple bilayer system, whereas skin has a highly complex lipid membrane architecture. Moreover, it is highly unlikely that a nanoparticle formulation applied on the skin will not have multiple nanoparticle-nanoparticle and skin-nanoparticle interactions. In this study, we have utilized coarse-grained MARTINI molecular dynamics simulations to assess the interactions of two types (bare and dodecane-thiol coated) of nanoparticles with two models (single bilayer and double bilayer) of skin lipid membranes. The nanoparticles were found to be partitioned from the water layer to the lipid membrane as an individual entity as well as in the cluster form. It was discovered that each nanoparticle reached the interior of both single bilayer and double bilayer membranes irrespective of the nanoparticle type and concentration, though coated particles were observed to efficiently traverse across the bilayer when compared with bare particles. The coated nanoparticles also created a single large cluster inside the membrane, whereas the bare nanoparticles were found in small clusters. Both the nanoparticles exhibited preferential interactions with cholesterol molecules present in the lipid membrane as compared to other lipid components of the membrane. We have also observed that the single membrane model exhibited unrealistic instability at moderate to higher concentrations of nanoparticles, and hence for translocation study, a minimum double bilayer model should be employed.
An aerodynamic study of industrial gas turbine exhaust turbines. (2005)

A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.
Ultrasound and shockwave therapy for acute fractures in adults (2012)

While a potential benefit of ultrasound for the treatment of acute fractures in adults cannot be ruled out, the currently available evidence from a set of clinically heterogeneous trials is insufficient to support the routine use of this intervention in clinical practice. Future trials should record functional outcomes and follow-up all trial participants.
Sol–Gel Derived Transparent Zirconium-Phenyl Siloxane Hybrid for Robust High Refractive Index LED Encapsulant (2014)

We report a zirconium-phenyl siloxane hybrid material (ZPH) that can be used as a robust LED encapsulant. The ZPH encapsulant was fabricated via hydrosilylation-curing of sol-gel derived multifunctional (vinyl- and hydride-functions) siloxane resins containing phenyl-groups and Zr-O-Si heterometallic phase for achieving a high refractive index (n ≈ 1.58). In thermal aging, the ZPH LED encapsulant exhibited superior performances with a high optical transparency (∼88% at 450 nm) and exhibited high thermal stability (no yellowing at 180 °C for 1008 h), compared to a commercial LED encapsulant (OE-6630, Dow Corning Corporation). This suggests potential for ZPH to be a robust LED encapsulant.
Web metadata standards: observations and prescriptions (2005)

The proliferation of Web metadata standards presents an opportunity to recall key lessons from related disciplines, such as software engineering, software reuse, library science, and knowledge representation. However, the haste to advance these standards also entails a danger that such lessons might be overlooked. In addition, the apparent confluence of metadata standards and artificial intelligence will likely yield mutual benefits but might also divert researchers' energies away from interoperability and other key issues. This article reviews various Web metadata standards and calls attention to lessons learned from related disciplines.
Serine Hydroxymethyltransferase from Solanum tuberosum (1995)

SHMT, EC 2.1.2.1, catalyzes the interconversion of Ser and Gly accompanied by the production or consumption of one-carbon units. In leaves it is a component of the photo- respiratory pathway (Keys et al., 1978). The main function of that pathway is the salvage of reduced carbon and nitrogen withdrawn from the Calvin cycle by the oxygen- ation of ribulose 1,5-bisphosphate. By the cooFeration of SHMT with the mitochondrial Gly cleavage system two molecules of Gly are converted into Ser, C02, and NH,. This reaction is considered to be the exclusive source of photorespiratory CO, release (Somerville and Ogren, 1981). The enzyme was first isolated from rabbit liver (Schirch and Mason, 1963) and, since then, has been studied in a variety of organisms and tissues. From human, cDNAs of both the cytosolic and the mitochondrial iso-SHMT were cloned (Garrow et al., 1993). In addition, the cloning of SHMT
Editor's Note (2011)

In 2009, Dr. Joachim Boldt published a manuscript in Anesthesia & Analgesia comparing albumin and hydroxyethyl starch priming cardiopulmonary bypass.1 A subsequent review by Landesärztekammer Rheinland-Pfalz (LÄ#K-RLP), the State Medical Association of Rheinland-Pfalz, determined that there was no IRB approval for the study. The article was retracted in December 2010.2 In response to the concerns regarding IRB approval LÄ#K-RLP investigated 103 additional manuscripts that included Dr. Boldt as a coauthor, including 23 manuscripts published in Anesthesia & Analgesia. Of these 23 articles, LÄ#K-RLP was able to verify IRB approval for only one.3 LÄ#K-RLP was unable to document IRB approval for the remaining 22 articles.4–25 Research without IRB approval is a violation of human rights. As described in our Guide for Authors,26 and a recent editorial,27Anesthesia & Analgesia requires IRB approval for all human research. There are no exceptions. The 22 manuscripts published by Dr. Boldt for which IRB approval has not been confirmed by LÄ#K-RLP are hereby retracted for unethical conduct of research. According to our publisher, the programs that link papers to retraction notices require a unique document identification number for each paper retracted. Therefore, this issue of Anesthesia & Analgesia contains 22 individual retraction notices representing the individual articles for which IRB approval has not been verified. Steven L. Shafer, MD Editor-in-Chief, Anesthesia & Analgesia Professor of Anesthesiology, Columbia University
Convergence of Asynchronous Distributed Gradient Methods Over Stochastic Networks (2017)

We consider distributed optimization problems in which a number of agents are to seek the global optimum of a sum of cost functions through only local information sharing. In this paper, we are particularly interested in scenarios, where agents are operating asynchronously over stochastic networks subject to random failures. Most existing algorithms require coordinated and decaying stepsizes to ensure zero gap between the estimated value of each agent and the exact optimum, restricting it from asynchronous implementation and resulting in slower convergence results. To deal with this issue, we develop a new asynchronous distributed gradient method (AsynDGM) based on consensus theory. The proposed algorithm not only allows for asynchronous implementation in a completely distributed manner but also, most importantly, is able to seek the exact optimum even with constant stepsizes. We will show that the assumption of boundedness of gradients, which is widely used in the literature, can be dropped by instead imposing the standard Lipschitz continuity condition on gradients. Moreover, we derive an upper bound of stepsize within which the proposed AsynDGM can achieve a linear convergence rate for strongly convex functions with Lipschitz gradients. A canonical example of sensor fusion problems is provided to illustrate the effectiveness of the proposed algorithm.
Inhibition of IP6K1 suppresses neutrophil-mediated pulmonary damage in bacterial pneumonia (2018)

The significance of developing host-modulating personalized therapies to counteract the growing threat of antimicrobial resistance is well-recognized because such resistance cannot be overcome using microbe-centered strategies alone. Immune host defenses must be finely controlled during infection to balance pathogen clearance with unwanted inflammation-induced tissue damage. Thus, an ideal antimicrobial treatment would enhance bactericidal activity while preventing neutrophilic inflammation, which can induce tissue damage. We report that disrupting the inositol hexakisphosphate kinase 1 (<i>Ip6k1</i>) gene or pharmacologically inhibiting IP6K1 activity using the specific inhibitor TNP [N2-(<i>m</i>-(trifluoromethyl)benzyl) N6-(<i>p</i>-nitrobenzyl)purine] efficiently and effectively enhanced host bacterial killing but reduced pulmonary neutrophil accumulation, minimizing the lung damage caused by both Gram-positive and Gram-negative bacterial pneumonia. IP6K1-mediated inorganic polyphosphate (polyP) production by platelets was essential for infection-induced neutrophil-platelet aggregate (NPA) formation and facilitated neutrophil accumulation in alveolar spaces during bacterial pneumonia. IP6K1 inhibition reduced serum polyP levels, which regulated NPAs by triggering the bradykinin pathway and bradykinin-mediated neutrophil activation. Thus, we identified a mechanism that enhances host defenses while simultaneously suppressing neutrophil-mediated pulmonary damage in bacterial pneumonia. IP6K1 is, therefore, a legitimate therapeutic target for such disease.
Digital and Social Media in Pro Sports: Analysis of the 2013 UEFA Top Four (2014)

Just like other businesses, so do professional sports teams use multi-functional websites and other online vehicles to connect to their audiences providing news, match day information, player statistics, and shopping opportunities among others. However, with the rapidly grown popularity of social media and mobile computing, the service expectations and functional requirements for digital online presence and interaction have also changed. We studied the characteristics of the 2013 UEFA top four football teams' online appearance, that is, the mix of official team websites and their social media and mobile applications. By building on past studies that had explored professional team websites by using the TEDS framework for information artifact evaluation, this investigation replicated the same 'human agent-centric' approach, but also included in the study the teams' social media and mobile channels. The results suggest that the official websites of the 2013 top-four UEFA teams have slightly improved over time. However, the official team websites have lost importance relative to social media and mobile channels.