gebhart/patrepeval huggingface dataset:
Mutations of the adenomatous polyposis coli gene in familial polyposis coli patients and sporadic colorectal tumors. (1991)

We have isolated several genes in the chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One of them (adenomatous polyposis coli; APC) was also found to mutate in the germ-line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer. Furthermore, in one colon carcinoma, we identified an interesting mechanism causing dysfunction of the APC gene. This gene was disrupted by a somatic insertion of a long interspersed repetitive element (LINE-1 sequence: L1) into the last exon. As an insertional sequence contains a 3' portion of the L1 consensus sequence including the poly(A) tract and an 8 bp target-site duplication was observed, this insertion is suspected to be caused by a retrotranscriptional insertion of one of the L1 sequences. This is the first case of the disruption of a tumor suppressor gene by the insertion of a movable genetic element.
ICT in multimodal transport and technological trends: Unleashing potential for the future (2014)

The role of information and communication technologies (ICTs) in freight transport as key enabler is well recognised. However the uptake of recent ICT advances for multimodal freight transport provisions in the UK and Europe has been slow. The aim of our paper is to explore the potential reasons for such a slow adoption and assess how recent technological advances such as cloud computing and Internet of Things might have changed the landscape and thus help to overcome these barriers. Via an extensive review of 33 EU framework programme projects, we are able to consolidate and present current major efforts in ICT developments in the freight multimodal transport setting at European level. We further discuss barriers inhibiting quick take-up of ICT applications in multimodal transport. Resolutions were then explored by reviewing four key ICT development trends recently emerging and evaluating their potential impact in reducing such barriers for deployment. Our contribution is two-fold: it advances current knowledge by presenting an up-to-date overview of existing and emerging ICT applications in the field of multimodal transport and barriers to e-enabled multimodal transport. It also captures some of the best practices in industry and aims to provoke a debate among practitioners and academics via the analysis of how innovative use of recent technological developments could potentially lower the barriers to multimodal ICT adoption and lead to a more integrated freight transport network. Therefore it lays the foundation for further research.
Elektronische Schalter (1977)

Ein idealer Schalter hat im Zustand EIN keinen wirksamen Widerstand zwischen seinen Klemmen und es fällt keine Spannung an ihm ab, wenn Strom fließt. Im Zustand AUS hat er einen unendlichen Widerstand zwischen seinen Klemmen und der Leckstrom ist Null. Darüberhinaus hat unser idealer Schalter ein perfektes Schaltverhalten, so daß die Zeit für das Ein- oder Ausschalten des Stromes Null ist.
Robust signal detection in 3D fluorescence microscopy (2009)

Robust detection and localization of biomolecules inside cells is of great importance to better understand the functions related to them. Fluorescence microscopy and specific staining methods make biomolecules appear as point-like signals on image data, often acquired in 3D. Visual detection of such point-like signals can be time consuming and problematic if the 3D images are large, containing many, sometimes overlapping, signals. This sets a demand for robust automated methods for accurate detection of signals in 3D fluorescence microscopy. We propose a new 3D point-source signal detection method that is based on Fourier series. The method consists of two parts, a detector, which is a cosine filter to enhance the point-like signals, and a verifier, which is a sine filter to validate the result from the detector. Compared to conventional methods, our method shows better robustness to noise and good ability to resolve signals that are spatially close. Tests on image data show that the method has equivalent accuracy in signal detection in comparison to visual detection by experts. The proposed method can be used as an efficient point-like signal detection tool for various types of biological 3D image data.
Design of Comparative Experiments (2008)

This book should be on the shelf of every practising statistician who designs experiments. Good design considers units and treatments first, and then allocates treatments to units. It does not choose from a menu of named designs. This approach requires a notation for units that does not depend on the treatments applied. Most structure on the set of observational units, or on the set of treatments, can be defined by factors. This book develops a coherent framework for thinking about factors and their relationships, including the use of Hasse diagrams. These are used to elucidate structure, calculate degrees of freedom and allocate treatment subspaces to appropriate strata. Based on a one-term course the author has taught since 1989, the book is ideal for advanced undergraduate and beginning graduate courses. Examples, exercises and discussion questions are drawn from a wide range of real applications: from drug development, to agriculture, to manufacturing.
Graphene oxide/silver nanoparticle ink formulations rapidly inhibit influenza A virus and OC43 coronavirus infection <i>in vitro</i> (2021)

Abstract Respiratory tract infections present a significant risk to the human population, both through seasonal circulation and novel introductions with pandemic potential. There is a strong need for antiviral compounds with broad antimicrobial activity that can be coated onto filtration systems and personal protective equipment to augment their ability to remove infectious particles from the environment. Graphene oxide and silver nanoparticles are both materials with documented antimicrobial properties. Here, we tested the in vitro antiviral properties of several graphene oxide–silver nanoparticle composite materials, which were prepared through three different methods: reduction with silver salt, direct addition of silver nanospheres, and direct addition of silver nanospheres to thiolized graphene. These materials were tested over short time scales for their antiviral activity against two enveloped RNA viruses, influenza A virus and OC43 coronavirus, by performing viral plaque assays after exposure of the viruses to each material. It was found that the graphene oxide – silver nanoparticle materials generated by direct addition of the silver nanospheres were able to completely inhibit plaque formation by both viruses within one minute of exposure. Materials generated by the other two methods had varying levels of efficacy against influenza A virus. These studies indicate that graphene oxide-silver nanoparticle composite materials can rapidly neutralize RNA viruses and demonstrate their potential for use in a wide range of applications. Abstract Figure
Melanoma Screening Using Deep Neural Networks (2018)

Deep learning algorithms, in particular convolutional neural networks, have rapidly become a methodology of choice for analyzing images. This choice arises due to fact that Deep Learning reduces the feature engineering task which is very important for automatic analysis of various kinds of images including medical images. In this work we have implemented various Deep Convolutional Neural Networks architectures for the process of binary classification task efficient enough in predicting either the input RGB image of the skin lesion is melanoma or not. Diagnosing the skin lesion is the first step towards its treatment. In this work we have assimilated two approaches on the pretrained Convolutional Neural Networks on the ImageNet dataset. Firstly, we use the transfer learning approach without any fine tuning and obtained features are fed for linear classification task. Secondly, we use the transfer learning approach with fine tuning. The adopted method requires no lesion segmentation or any other higher level image processing tasks. Finally, we have also developed a real time android application to perform the binary classification task. The result obtained using our android application were enthusiastic.
Medical care output and productivity (2001)

We review in considerable detail the conceptual and measurement issues that underlie construction of medical care price indexes in the U.S., particularly the medical care consumer price indexes (MCPIs) and medical-related producer price indexes (MPPIs). We outline salient features of the medical care marketplace, including the impacts of insurance, moral hazard, principal-agent relationships, technological progress and organizational changes. Since observed data are unlikely to correspond with efficient outcomes, we discuss implications of the failure of transactions data in this market to reveal reliable marginal valuations, and the consequent need to augment traditional transactions data with information based on cost-effectiveness and outcomes studies. We describe procedures currently used by the BLS in constructing MCPIs and MPPIs, including recent revisions, and then consider alternative notions of medical care output pricing that involve the price or cost of an episode of treatment, rather than prices of fixed bundles of inputs. We outline features of a proposed new experimental price index -- a medical care expenditure price index -- that is more suitable for evaluation and analyses of medical care cost changes, than are the current MCPIs and MPPIs. We conclude by suggesting future research and measurement issues that are most likely to be fruitful.
Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review. (2011)

The National Institute for Health Research Health Technology Assessment programme.
A phase 1b study in cutaneous T-cell lymphoma (CTCL) with the novel topically applied skin-restricted histone deacteylase inhibitor (HDAC-i) SHP-141. (2014)

8525 Background: The efficacy of HDAC-i as systemic therapy in CTCL is well-established although adverse effects limit use. The topical hydroxamic acid HDAC-i SHP-141 is intentionally designed to maximize activity in skin but limit systemic exposure by rendering the drug inactive via endogenous serum esterases. Methods: A phase 1b multi-center, double-blind, placebo (PBO)-controlled, randomized trial in stage IA-IIA CTCL was conducted in the USA to assess safety, pharmacokinetic (PK), pharmacodynamic, and preliminary efficacy with SHP-141 applied twice daily to index lesions (maximum 5% BSA) for 28 days; last assessment was 42 days after start of drug. Eighteen patients were enrolled: 6 patients (5 SHP-141:1 PBO) at each escalating dose level (0.1%, 0.5%, 1.0%). In SHP-141 arms there were 3 patients with stage IA, 11 IB, and 1 IIA; PBO arm with 2 stage IA and 1 IB. Results: No DLTs, early discontinuations, serious adverse events (AEs) or systemic AEs were recorded; SHP-141 related events were predominantly CTCAE Grade 1 and limited to skin (Skin, SHP-141: 4/15, PBO: 1/3; 1 CTCAE Grade 2 dermatitis in SHP-141). Only SHP-141 patients had clinical objective response (OR; >50% improvement by CAILS) and incremental weekly CAILS improvement through dosing period (see Table). Time to OR occured as early as Day 7; 2 others at Day 21 with the last at Day 42. Based on CAILS subscore a significant reduction in lesion thickness for SHP-141 groups was measured. Skin biopsy histology confirmed increased dermal actetylation by staining with a specific acetyl–lysine antibody. PK results confirmed lack of SHP-141 peripheral blood exposure. Conclusions: This is the first skin-optimized topical HDAC-i with evidence of early clinical activity and without systemic HDAC-i related toxicity. Patients responded after few weeks of treatment; rapidity is not a typical feature of approved topical drugs for CTCL. SHP-141 may address an important unmet medical need in early stage CTCL by feasibly offering clinical benefits of a HDAC-i without safety concerns. Clinical trial information: NCT01433731. SHP-141 Placebo Objective response at day 42 4(28%) 0 Reduction in thickened lesions at day 42 89% 0% Incremental improvement to day 28 6(40%) 0
The Kinetics of Heat-Induced Structural Changes of β-Lactoglobulin (2005)

Heat-induced structural changes of beta-lactoglobulin were studied at temperatures ranging from 67.5 to 82.5 degrees C, and at pH 7.5. These changes were monitored by measurement of surface hydrophobicity, thiol availability, and protein solubility. Kinetic studies were conducted to quantitatively describe the contribution of hydrophobic and SH/SS interchange reactions to the thermal structural changes of beta-lactoglobulin. Results indicate that beta-lactoglobulin is sensitive to heat-induced interchange reactions with consequences for protein solubility. The extent of changes measured by the increase in surface hydrophobicity and the decrease in slow-reacting SH groups content could be described by a first-order fractional conversion model and were characterized by activation energy values of 233.9 +/- 8.6 and 148.2 +/- 6.7 kJ/mol, respectively. The break in the Arrhenius plot suggested in literature for beta-lactoglobulin denaturation was confirmed in this study only for the kinetics of exposed SH groups.
Towards effective AI-powered agile project management (2018)

The rise of Artificial intelligence (AI) has the potential to significantly transform the practice of project management. Project management has a large socio-technical element with many uncertainties arising from variability in human aspects e.g., customers' needs, developers' performance and team dynamics. AI can assist project managers and team members by automating repetitive, high-volume tasks to enable project analytics for estimation and risk prediction, providing actionable recommendations, and even making decisions. AI is potentially a game changer for project management in helping to accelerate productivity and increase project success rates. In this paper, we propose a framework where AI technologies can be leveraged to offer support for managing agile projects, which have become increasingly popular in the industry.
Algebraic Coding Theory: Revised Edition (2015)

This is the revised edition of Berlekamp's famous book, Algebraic Coding Theory, originally published in 1968, wherein he introduced several algorithms which have subsequently dominated engineering practice in this field. One of these is an algorithm for decoding Reed-Solomon and BoseChaudhuriHocquenghem codes that subsequently became known as the BerlekampMassey Algorithm. Another is the Berlekamp algorithm for factoring polynomials over finite fields, whose later extensions and embellishments became widely used in symbolic manipulation systems. Other novel algorithms improved the basic methods for doing various arithmetic operations in finite fields of characteristic two. Other major research contributions in this book included a new class of Lee metric codes, and precise asymptotic results on the number of information symbols in long binary BCH codes. Selected chapters of the book became a standard graduate textbook. Both practicing engineers and scholars will find this book to be of great value. Readership: Researchers in coding theory and cryptography, algebra and number theory, and software engineering.
Delivery of Chicken Egg Ovalbumin to Dendritic Cells by Listeriolysin O-Secreting Vegetative Bacillus subtilis (2018)

Listeriolysin O (LLO), one of the most immunogenic proteins of <i>Listeria monocytogenes</i> and its main virulence factor, mediates bacterial escape from the phagosome of the infected cell. Thus, its expression in a nonpathogenic bacterial host may enable effective delivery of heterologous antigens to the host cell cytosol and lead to their processing predominantly through the cytosolic MHC class I presentation pathway. The aim of this project was to characterize the delivery of a model antigen, chicken egg ovalbumin (OVA), to the cytosol of dendritic cells by recombinant <i>Bacillus subtilis</i> vegetative cells expressing LLO. Our work indicated that LLO produced by non-sporulating vegetative bacteria was able to support OVA epitope presentation by MHC I molecules on the surface of antigen presenting cells and consequently influence OVA-specific cytotoxic T cell activation. Additionally, it was proven that the genetic context of the epitope sequence is of great importance, as only the native full-sequence OVA fused to the N-terminal fragment of LLO was sufficient for effective epitope delivery and activation of CD8⁺ lymphocytes. These results demonstrate the necessity for further verification of the fusion antigen potency of enhancing the MHC I presentation, and they prove that LLO-producing <i>B. subtilis</i> may represent a novel and attractive candidate for a vaccine vector.
Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7 (2021)

Facioscapulohumeral muscular dystrophy (FSHD) is characterised by progressive skeletal muscle weakness and wasting. FSHD is linked to epigenetic derepression of the subtelomeric D4Z4 macrosatellite at chromosome 4q35. Epigenetic derepression permits the distal-most D4Z4 unit to transcribe DUX4, with transcripts stabilised by splicing to a poly(A) signal on permissive 4qA haplotypes. The pioneer transcription factor DUX4 activates target genes that are proposed to drive FSHD pathology. While this toxic gain-of-function model is a satisfying "bottom-up" genotype-to-phenotype link, DUX4 is rarely detectable in muscle and DUX4 target gene expression is inconsistent in patients. A reliable biomarker for FSHD is suppression of a target gene score of PAX7, a master regulator of myogenesis. However, it is unclear how this "top-down" finding links to genomic changes that characterise FSHD and to DUX4. Here, we explore the roles and interactions of DUX4 and PAX7 in FSHD pathology and how the relationship between these two transcription factors deepens understanding via the immune system and muscle regeneration. Considering how FSHD pathomechanisms are represented by "DUX4opathy" models has implications for developing therapies and current clinical trials.
Thermal-Structural Design/Analysis of an Airframe-Integrated Hydrogen-Cooled Scramjet (1976)

This paper presents the salient features of a preliminary thermal-structural design and analysis study of a hydrogen-fueled, regeneratively cooled, airframe-integrated scramjet. This three-dimensional fixed geometry scramjet concept, which was developed at NASA Langley Research Center, is designed to operate over a flight Mach number range from 4 to 10. The thermal-structural study was focused on a scramjet application to one concept for a hypersonic research vehicle and was based on technology developed under the NASA Hypersonic Research Engine Project. State-of-the-art analytical methods consisting of lumped system and finite-difference steady-state thermal analyses and a finite-element structural analysis were used. The results of the study indicated that this scramjet concept is viable from both a structural mass and cooling requirement standpoint. However, advances in material and fabrication technology for hydrogen-cooled structures appear necessary for acceptable engine life for commercial application.
Hypoxia-inducible transcription factor-1α promotes hypoxia-induced A549 apoptosis via a mechanism that involves the glycolysis pathway (2006)

During hypoxia in A549 cells, HIF-1alpha promotes activity of the glycolysis pathway and decreases the pH of the culture medium, resulting in increased cellular apoptosis.
Ionic Liquids as Versatile Precursors for Functionalized Porous Carbon and Carbon–Oxide Composite Materials by Confined Carbonization (2010)

Manche mögen's heiß: Die Thermolyse einer ionischen Flüssigkeit (IL) ergibt keine Verbrennungsrückstände, während ein Erhitzen derselben IL in einem Oxidgerüst hohe Carbonisierungsausbeuten liefert (siehe Bild). Dies ermöglicht den Einbau von Heteroatomen aus der IL in die Endprodukte zur Entwicklung funktionalisierter poröser Kohlenstoff- und Kohlenstoff-Oxid-Kompositmaterialien.
Effects of BCL-2 antisense oligodeoxynucleotides on in vitro proliferation and survival of normal marrow progenitors and leukemic cells (1994)

Previous studies have shown that the BCL-2 protooncogene encodes a mitochondrial protein that promotes cell survival by blocking programmed cell death. Bcl-2 protein has been detected in normal immature myeloid cells and in acute myeloid leukemia (AML) cells. To assess its functional role in normal and leukemic hematopoiesis, we performed serum-free cultures of CD34+ normal marrow cells, of bcl-2- positive myeloid lines, and of AML cells in the presence of bcl-2 sense, nonsense, and antisense phosphorothioate oligodeoxynucleotides. In all antisense-treated cultures, we observed (1) an inhibition of bcl- 2 protein expression by day 4 to 6 of culture; (2) a decrease in cell survival duration; and (3) a decrease in the number of clonogenic cells present in the culture. Moreover, exposure to chemotherapeutic drugs resulted in more effective killing of AML cells in the presence of antisense oligomers. We conclude that bcl-2 protein is necessary for the survival of myeloid cells in culture, and that it may be implicated in the resistance of AML cells to chemotherapy.
The Protein Kinase Domain of the ANP Receptor Is Required for Signaling (1989)

A plasma membrane form of guanylate cyclase is a cell surface receptor for atrial natriuretic peptide (ANP). In response to ANP binding, the receptor-enzyme produces increased amounts of the second messenger, guanosine 3',5'-monophosphate. Maximal activation of the cyclase requires the presence of adenosine 5'-triphosphate (ATP) or nonhydrolyzable ATP analogs. The intracellular region of the receptor contains at least two domains with homology to other proteins, one possessing sequence similarity to protein kinase catalytic domains, the other to regions of unknown function in a cytoplasmic form of guanylate cyclase and in adenylate cyclase. It is now shown that the protein kinase-like domain functions as a regulatory element and that the second domain possesses catalytic activity. When the kinase-like domain was removed by deletion mutagenesis, the resulting ANP receptor retained guanylate cyclase activity, but this activity was independent of ANP and its stimulation by ATP was markedly reduced. A model for signal transduction is suggested in which binding of ANP to the extracellular domain of its receptor initiates a conformational change in the protein kinase-like domain, resulting in derepression of guanylate cyclase activity.