gebhart/patrepeval huggingface dataset:
Late‐onset neurodegenerative diseases—the role of protein insolubility (2000)

Recently, mutations of the alpha-synuclein gene were found to cause dominantly inherited Lewy-body Parkinson's disease (PD) and alpha-synuclein was identified as a major component of the Lewy body. However, the cause of the common form of PD, with a multifactorial rather than autosomal dominant inheritance pattern, remains unknown. Alpha-synuclein precipitates slowly and apparently spontaneously at high concentration in solution and the mutations that cause PD accelerate precipitation. Other dominantly inherited late-onset or adult-onset dominantly inherited neurodegenerative diseases are associated with precipitation of proteins. In Alzheimer disease, beta-amyloid and tau abnormalities are present and in prion disorders, prion proteins are found. In Huntington disease, a disorder with expanded CAG repeats, huntingtin precipitates occur. In dominantly inherited spinocerebellar ataxias, also expanded CAG repeat disorders, the corresponding ataxin protein precipitates are found. In multiple system atrophy, alpha-synuclein precipitates are encountered and in progressive supranuclear palsy, tau precipitates occur. In familial amyotrophic lateral sclerosis, a group of dominantly inherited disorders, SOD1 precipitates are found. Most of these disorders can involve the basal ganglia in some way. Since similar processes seem to affect neurons of adults or older individuals and since a relatively limited group of proteins seems to be involved, each producing a form of neurodegeneration, it is possible that certain common features are present that affect this group of proteins. Candidates include a conformational shift, as in prions, an abnormality of the ubiquitin-proteosome pathway, as seen in PD, an abnormality of a pathway preventing precipitation (e.g. chaperonins), or potentiation of a pathway promoting precipitation (e.g. gamma-glutamyl-transpeptidase) or apoptosis. Elucidation of the pathways causing this protein insolubilisation is the first step towards approaching prevention and reversal in these late-onset neurodegenerative diseases.
Individual Human Phenotypes in Metabolic Space and Time (2009)

Differences between individual phenotypes are due both to differences in genotype and to exposure to different environmental factors. A fundamental contribution to the definition of the individual phenotype for clinical and therapeutic applications would come from a deeper understanding of the metabolic phenotype. The existence of unique individual metabolic phenotypes has been hypothesized, but the experimental evidence has been only recently collected. Analysis of individual phenotypes over the timescale of years shows that the metabolic phenotypes are largely invariant. The present work also supports the idea that the individual metabolic phenotype can also be considered a metagenomic entity that is strongly affected by both gut microbiome and host metabolic phenotype, the latter defined by both genetic and environmental contributions.
Painful data: The UNBC-McMaster shoulder pain expression archive database (2011)

A major factor hindering the deployment of a fully functional automatic facial expression detection system is the lack of representative data. A solution to this is to narrow the context of the target application, so enough data is available to build robust models so high performance can be gained. Automatic pain detection from a patient's face represents one such application. To facilitate this work, researchers at McMaster University and University of Northern British Columbia captured video of participant's faces (who were suffering from shoulder pain) while they were performing a series of active and passive range-of-motion tests to their affected and unaffected limbs on two separate occasions. Each frame of this data was AU coded by certified FACS coders, and self-report and observer measures at the sequence level were taken as well. This database is called the UNBC-McMaster Shoulder Pain Expression Archive Database. To promote and facilitate research into pain and augment current datasets, we have publicly made available a portion of this database which includes: (1) 200 video sequences containing spontaneous facial expressions, (2) 48,398 FACS coded frames, (3) associated pain frame-by-frame scores and sequence-level self-report and observer measures, and (4) 66-point AAM landmarks. This paper documents this data distribution in addition to describing baseline results of our AAM/SVM system. This data will be available for distribution in March 2011.
Translating BPMN to BPEL (2006)

Abstract. The Business Process Modelling Notation (BPMN) is a graphoriented language in which control and action nodes can be connected almost arbitrarily. It is supported by various modelling tools but so far no systems can directly execute BPMN models. The Business Process Execution Language for Web Services (BPEL) on the other hand is a mainly block-structured language supported by several execution platforms. In the current setting, mapping BPMN models to BPEL code is a necessary step towards unified and standards-based business process development environments. It turns out that this mapping is challenging from a scientific viewpoint as BPMN and BPEL represent two fundamentally different classes of languages. Existing methods for mapping BPMN to BPEL impose limitations on the structure of the source model, especially with respect to cycles. This report proposes a technique that overcomes these limitations. Beyond its direct relevance in the context of BPMN and BPEL, this technique addresses difficult problems that arise generally when translating between flow-based languages with parallelism. 1
In-line fiber Fabry-Perot interferometer with high-reflectance internal mirrors (1992)

A finesse of 21 has been measured for a fiber Fabry-Perot interferometer (FFPI) with multilayer TiO/sub 2//SiO/sub 2/ internal mirrors. Experimental reflectance and transmittance data for the thermally tuned interferometer were fit with calculated curves using values of 86% for the reflectance and 7.2% (0.33 dB) for the excess optical loss of each mirror. Applications in sensing and communications are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Inhibition of proteasome function induced apoptosis in gastric cancer (2001)

The ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines AGS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132. The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. AGS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by the activation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP. Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 in AGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result of release of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53, p21(waf1) and p27(kip1) at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G(1) phase. Our present study suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer.
Gravity measurements on the moon (2000)

The late Lucien J. B. LaCoste (1908–1995) successfully designed gravity meters for nearly every environment on earth—from marine to airborne, from land to underwater to the borehole. This made him an obvious choice for the ultimate challenge in the 1970s, designing a gravity meter for the moon. This is the story of the lunar gravity meter and how a simple error caused it to fail.
GIS and Crime Mapping (2005)

GIS and Crime Mapping is the definitive text to support readers with the fundamental theory, scientific methodologies, analysis techniques, application design, and management processes for implementing and developing crime mapping. The book includes a comprehensive presentation of GIS, crime mapping and geographic crime analysis solutions for operational, tactical, investigative, and strategic policing and crime reduction purposes. Topics in this book include, • The basics of GIS for mapping crime • Definitions and geographical structures within criminal justice • The principle spatial theories of crime • Spatial statistics for crime analysis • Crime hotspots • Mapping and analysing change over time • Mapping crime with local community data • Information sharing • GIS and crime mapping for operational, tactical, investigative, and strategic policing and crime reduction • Crime map cartography • Implementing GIS and crime mapping • Managing and organising crime mapping and analysis. GIS and Crime Mapping draws from the authors’ international expertise and experiences. The book includes short case studies at relevant sections to help demonstrate the key principles, concepts and applications of crime mapping, and bring an added international richness and depth. GIS and Crime Mapping uniquely combines the topics of theoretical principles, GIS, analysis, map design, and organisational structures of GIS and crime mapping for policing and crime reduction, delivered in a style that is accessible to a broad range of readers. These include intelligence and crime analysts; policing, intelligence, law enforcement and crime reduction practioners; and academics, lecturers, researchers and students in GIS, crime science, crime prevention, community safety, criminal justice or criminology. GIS and Crime Mapping acts as an important and timely book in this growing and exciting field.
Principles of stable isotope research – with special reference to protein metabolism (2021)

The key to understanding the mechanisms regulating disease stems from the ability to accurately quantify the dynamic nature of the metabolism underlying the physiological and pathological changes occurring as a result of the disease. Stable isotope tracer technologies have been at the forefront of this for almost 80 years now, and through a combination of both intense theoretical and technological development over these decades, it is now possible to utilise stable isotope tracers to investigate the complexities of in vivo human metabolism from a whole body perspective, down to the regulation of sub-nanometer cellular components (i.e organelles, nucleotides and individual proteins). This review therefore aims to highlight; 1) the advances made in these stable isotope tracer approaches - with special reference given to their role in understanding the nutritional regulation of protein metabolism, 2) some considerations required for the appropriate application of these stable isotope techniques to study protein metabolism, 3) and finally how new stable isotopes approaches and instrument/technical developments will help to deliver greater clinical insight in the near future.
CHEMOPREVENTION OF LUNG CANCER BY ISOTHIOCYANATES AND THEIR CONJUGATES IN A/J MOUSE (2001)

The discovery of dietary-related compounds with potential to inhibit lung cancer may present promising and practical approaches for reducing the risk of lung cancer caused by smoking. To this end, we have conducted mechanism-based bioassays in A/J mice over the years to screen compounds, particularly isothiocyanates (ITCs) in the crucifer family, and studied their modes of action against lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a nicotine-derived lung carcinogen. These studies have shown that A/J mice serve as a practical and useful model for the study of lung cancer prevention. The studies described here illustrate the value of using the A/J mouse model in the bioassays and the structural-activity relationship, metabolism, and mechanism investigations. One of the important features of the A/J mouse model is that a single dose of NNK induces a significant number of lung tumors within 16 weeks. This feature offers a prerequisite for in vivo screening as well as for dissecting the initiation or the postinitiation effect of ITCs and their conjugates during lung tumor development. Our recent bioassays in A/J mice demonstrate that ITC conjugates are versatile chemopreventive agents capable of inhibiting NNK-induced lung tumorigenesis during both the initiation and the postinitiation phases. These findings are of importance, considering the potential of these agents as chemopreventive agents for lung cancer in smokers and ex-smokers.
A fast dual‐energy computational method using isotransmission lines and table lookup (1987)

An efficient method has been developed to speed up the computational time required for tissue separation after the dual-energy scan in computerized tomography and digital radiography. This method consists of two steps. First, an isotransmission line method is used to replace the iterative algorithm for solving the two nonlinear equations, which is computationally noisy and sensitive. Second, two tables, one for the aluminum component and the other for the plastic component, are derived from calibration data in order to replace calculation by a table lookup. Results from this method are compared with the conventional method.
Object‐oriented switching program structure (1992)

Abstract Public switching systems are severely real‐time and multiprocessing, very large, long‐lived, and frequently modified. Programs that control switching systems therefore are required not only to have run‐time efficiency but also to be easy to maintain and expand. This paper proposes a concurrent object model and an object‐oriented switching program structure. The concurrent object model ensures simple and efficient real‐time multiprocessing. Also, it allows logical switching components to be implemented as “objects” in software, and the structure of the program coincides with the structure of the logical model. The program structure proposed here uses distributed call processing, which allows building‐block structured switching systems. A prototype switching program confirmed the effectiveness of this approach and showed that the static and dynamic overheads are within the capacity of present VLSI technology.
Processos linfoproliferativos da pele: parte 2 - linfomas cutâneos de células T e de células NK (2006)

Os linfomas cutâneos de células T/NK constituem um grupo de doenças linfoproliferativas extranodais atualmente classificadas e subdivididas de acordo com o comportamento clínico segundo consenso da Organização Mundial de Saúde e da Organização Européia para Pesquisa e Tratamento do Câncer. Os linfomas cutâneos de células T/NK de comportamento clínico indolente compreendem a micose fungóide clássica, a micose fungóide foliculotrópica, a reticulose pagetóide, a cútis laxa granulomatosa, o linfoma cutâneo primário de grande célula anaplásica, a papulose linfomatóide, o linfoma subcutâneo de célula T paniculite-símile e o linfoma cutâneo primário de pequena e média célula T CD4+ pleomórfica. Os linfomas cutâneos de células T/NK de comportamento agressivo incluem a síndrome de Sézary, o linfoma extranodal de célula T/NK, tipo nasal, o linfoma cutâneo primário agressivo de célula T CD8+ epidermotrópica, o linfoma cutâneo de célula T <FONT FACE=Symbol>gd</FONT> e o linfoma cutâneo primário de célula T periférica, não especificado. O linfoma-leucemia de células T do adulto e a neoplasia hematodémica CD4+CD56+, embora considerados linfomas sistêmicos, são aqui abordados por apresentarem-se inicialmente na pele em significativo número de pacientes. O diagnóstico desses processos é realizado pelo exame histopatológico complementado pela análise do fenótipo das células neoplásicas, imprescindível no processo classificatório. O estadiamento para a avaliação da extensão anatômica da doença considera além do envolvimento cutâneo, o estado clínico e histológico dos linfonodos e das vísceras. Avaliação hematológica é fundamental na caracterização da síndrome de Sézary. Os tratamentos preconizados incluem terapêuticas dirigidas exclusivamente à pele, modificadores da resposta biológica e quimioterapia sistêmica.
Persistence and Protective Efficacy of a <i>Mycobacterium tuberculosis</i> Auxotroph Vaccine (1999)

New vaccines against tuberculosis are urgently required because of the impressive incidence of this disease worldwide and the highly variable protective efficacy of the current vaccine. The possibility of creating new live vaccines by the rational attenuation of strains from the Mycobacterium tuberculosis complex was investigated. Two auxotrophic mutants of M. tuberculosis and M. bovis BCG were constructed by disruption of one of their purine biosynthetic genes. These mutants appeared unable to multiply in vitro within mouse bone-marrow derived macrophages. They were also attenuated in vivo in the mouse and guinea pig animal models. In guinea pigs, the two mutants induced strong delayed-type hypersensitivity response to purified protein derivative. In a preliminary experiment, the two mutants were compared to the BCG vaccine for their protective efficacy in a challenge against aerosolized virulent M. tuberculosis in the guinea pig model. Both mutants conferred some level of protection. These experiments demonstrate that the rational attenuation of M. tuberculosis could lead to the design of new candidate live vaccines against tuberculosis.
Ultracentrifugation of salt‐soluble proteins in ten legume species (1979)

Abstract The ultracentrifugation patterns of the total salt‐soluble proteins in pea and northern bean showed four globulin fractions in flour proteins but only the 2S, 7S and 9S globulins were found in the isolates. Mung bean, lentil and lupin exhibited 2S, 7S and 11S globulins in flour and isolate proteins while chick‐pea, field‐pea, faba‐bean and soya‐bean proteins also contained the 15S fraction. Salt‐soluble proteins from lima bean were unique in their composition of 5S, 7S and 15S fractions. Only pea bean and lentil failed to show high proportions of the 1‐5S fraction in the flour proteins.
A Review of Recent Patents Concerning Therapy of Respiratory Diseases Using Gene Silencing by RNAi (RISC) and EGS (RNAse P) (2007)

This article will review recent developments in the field of gene silencing as a therapy for respiratory and related inflammatory and immunologic diseases. The respiratory epithelium offers an attractive target for therapies derived from nucleic acids since the respiratory epithelium contains endogenous lipids that can facilitate uptake of polar nucleic acids and related compounds. Both RNAi (RNA Interference) in which a messenger RNA (mRNA) is targeted by an endogenous enzyme complex termed RISC (RNA Interference Silencing Complex, also previously termed RNA Induced Silencing Complex in earlier references) and also gene silencing using EGS (External Guide Sequences) in which a messenger RNA (mRNA) is targeted by an endogenous RNA enzyme termed RNase P are summarized including selected patents. The strengths and limitations of these technologies such as problems of delivery to specific tissues and potential for non-specific inflammatory response and off-targeting are compared. The possibility of therapy designed exploit synergies between both RISC and RNAse P and therapeutic benefits of inhibiting either or both pathways are also considered.
Mifepristone in combination with methotrexate for the medical treatment of tubal pregnancy: a randomized, controlled trial (1998)

In the search for a more potent alternative to a single i.m. injection of methotrexate for ectopic pregnancy, a randomized trial was organized. The efficacy of a combination of methotrexate and mifepristone was compared with methotrexate alone in the treatment of unruptured tubal pregnancies. The diagnosis of an unruptured tubal pregnancy was confirmed laparoscopically in 50 patients during a 2 year period. Women were randomized to receive a single i.m. injection of 50 mg/m2 methotrexate alone or a single dose of 600 mg oral mifepristone in combination with the same dose of methotrexate. Both treatment protocols were successful in achieving the resolution of unruptured ectopic pregnancy (18/25 in the methotrexate group and 22/25 in the combination group) following the initial intervention. A second injection was needed in four (16%) cases in the methotrexate group and in one (4%) case in the combination group. Overall, a complete resolution was achieved in 22/25 and 23/25 cases respectively. Unruptured ectopic pregnancy resolved faster in women given the combination of methotrexate and mifepristone compared to women given methotrexate only (P = 0.01). The effect of the methotrexate and mifepristone combination was more pronounced in women with higher human chorionic gonadotrophin concentrations.
Multiple significance tests: the Bonferroni method (1995)

<h3>Abstract</h3> Recent studies have shown that p53 contributes to poor survival during immune checkpoint blockade (ICB) therapy. Lung cancer patients with p53 mutations have significantly improved response rates to PD-1 ICB therapy. While previous studies have shown that tumor-derived IL-33 is required for the anti-tumor immune response and efficacy of ICB therapies, the relationship between p53 and IL-33 during ICB therapy is unknown. In this study, we characterized the role of the p53/IL-33 axis in regulating the tumor microenvironment (TME) in response to ICB therapy. CRISPR-Cas9-mediated deletion of Trp53 in tumor cells combined with PD-1 ICB therapy synergistically inhibited tumor growth in a murine MC38 colon adenocarcinoma model. We observed increased CD4+ and CD8+ T cell infiltration, as well as reduced Treg infiltration. IL-33 was upregulated and its expression increased with time and response to treatment. Simultaneous deletion of Il33 in the MC38 tumor cells reversed the efficacy of PD-1 ICB therapy. ST2<sup>-/-</sup>(IL-33 receptor) mice with Trp53-deficient MC38 tumors also showed no response to PD-1 ICB. Our findings depict a novel mechanism by which the loss of p53 in tumors treated with ICB therapy induces upregulation of tumoral IL-33 and host ST2 signaling. p53 mutations may be a double-edged sword for cancer, i.e. loss of the tumor suppressor initially facilitates tumorigenesis, but also leads to upregulation of danger signals in the tumor. These danger signals, such as IL-33, mediate the anti-tumor effect of ICB.