gebhart/patrepeval huggingface dataset:
ErbB Family Signalling: A Paradigm for Oncogene Addiction and Personalized Oncology (2017)

ErbB family members represent important biomarkers and drug targets for modern precision therapy. They have gained considerable importance as paradigms for oncoprotein addiction and personalized medicine. This review summarizes the current understanding of ErbB proteins in cell signalling and cancer and describes the molecular rationale of prominent cases of ErbB oncoprotein addiction in different cancer types. In addition, we have highlighted experimental technologies for the development of innovative cancer cell models that accurately predicted clinical ErbB drug efficacies. In the future, such cancer models might facilitate the identification and validation of physiologically relevant novel forms of oncoprotein and non-oncoprotein addiction or synthetic lethality. The identification of genotype-drug response relationships will further advance personalized oncology and improve drug efficacy in the clinic. Finally, we review the most important drugs targeting ErbB family members that are under investigation in clinical trials or that made their way already into clinical routine. Taken together, the functional characterization of ErbB oncoproteins have significantly increased our knowledge on predictive biomarkers, oncoprotein addiction and patient stratification and treatment.
The use of linguistic hierarchies in speech understanding (1998)

This paper describes two related systems which provide frameworks for encoding linguistic knowledge into formal rules within the context of a trainable probabilistic model. The first system, TINA [33], drives top-down from sentence level structure, terminating in either words or syllables. Its main purpose is to provide a meaning representation for the sentence. The other system, ANGIE [36], operates bottom-up from phonetic or orthographic units, characterizing the substructure of syllables/words. It provides a framework for both phonological rule modelling and letter-to-sound/sound-to-letter transformations. The two systems logically converge on the syllable or word layer. We have recently been successful in integrating their combined constraint into a recognizer search, achieving considerable improvement in understanding accuracy [9, 23]. In this paper, I will look both toward the past and the future, identifying and motivating the decisions that were made in the design of TINA and ANGIE and the associated rule formalisms, and contemplating various remaining open research issues.
Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca <sup>2+</sup> homeostasis (2013)

Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease.
The Contribution of NMR, NIRS and their Combination to the Functional Assessment of Human Muscle (1997)

In the last decade the study of the human muscle mechanics and energetics in physiology and pathology underwent a radical change. Indeed, the use of biopsy is being progressively accompanied by non-invasive techniques which allow a more integrative assessment of muscle function in vivo. Magnetic resonance imaging (MRI) provides a better insight into muscle structure down to the fascicular level, proving to be an essential source of information, particularly for the study of biomechanics. Magnetic resonance spectroscopy (MRS), besides the study of muscle anaerobic (high energy phosphate compounds by 31P and 1H) and aerobic metabolism as well as of metabolic control, makes it possible to follow the time course of glycogen concentration (13C) as a function of exercise intensity and duration and of its recovery both in healthy trained and untrained subjects and in diabetic patients. Near-infrared spectroscopy (NIRS) allows to assess muscle oxidative metabolism, providing changes of total, deoxy- and oxy-hemoglobin in the resting and contracting muscle. The concomitant use of the above techniques is expected to provide a synergic functional picture of the human muscle that is complementary to the structural and ultrastructural microscopic approach.
A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination (2014)

The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5-dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program.
Orthopaedic metals and their potential toxicity in the arthroplasty patient (2007)

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.
3D registration based perception in augmented reality environment (2016)

Abstract Early augmented reality (AR) community has paid a lot of attention to identifying 2D fiducial markers in AR scene, only a little works have been devoted to 3D objects perception. With the massively increased usage of 3D representation, it is highly desirable that powerful processing tools and algorithms should be developed for 3D recognition purpose in the augmented reality domain. In this paper, we address the 3D depth understanding problem for AR assembly applications. We propose a 3D registration based perception method designed for desk assembly environments. The 3D perception method involves two tasks: the optical flow based structure from motion (SFM) and a coplanar 4 points set registration of the SFM point cloud and CAD models point cloud. From the transformation, the position and orientation of the real industrial object in the assembly environment can be determined and an AR operation can be applied. The novelty of our method resides in that it does not require any marker attached on the scene and obtain a more accurate registration result.
Formation of<i>Streptococcus pneumoniae</i>Non-Phase-Variable Colony Variants Is Due to Increased Mutation Frequency Present under Biofilm Growth Conditions (2008)

In this report, we show that biofilm formation by Streptococcus pneumoniae serotype 19 gives rise to variants (the small mucoid variant [SMV] and the acapsular small-colony variant [SCV]) differing in capsule production, attachment, and biofilm formation compared to wild-type strains. All biofilm-derived variants harbored SNPs in cps19F. SCVs reverted to SMV, but no reversion to the wild-type phenotype was noted, indicating that these variants were distinct from opaque- and transparent-phase variants. The SCV-SMV reversion frequency was dependent on growth conditions and treatment with tetracycline. Increased reversion rates were coincident with antibiotic treatment, implicating oxidative stress as a trigger for the SCV-SMV switch. We, therefore, evaluated the role played by hydrogen peroxide, the oxidizing chemical, in the reversion and emergence of variants. Biofilms of S. pneumoniae TIGR4-DeltaspxB, defective in hydrogen peroxide production, showed a significant reduction in variant formation. Similarly, supplementing the medium with catalase or sodium thiosulfate yielded a significant reduction in variants formed by wild-type biofilms. Resistance to rifampin, an indicator for mutation frequency, was found to increase approximately 55-fold in biofilms compared to planktonic cells for each of the three wild-type strains examined. In contrast, TIGR4-DeltaspxB grown as a biofilm showed no increase in rifampin resistance compared to the same cells grown planktonically. Furthermore, addition of 2.5 and 10 mM hydrogen peroxide to planktonic cells resulted in a 12- and 160-fold increase in mutation frequency, respectively, and gave rise to variants similar in appearance, biofilm-related phenotypes, and distribution of biofilm-derived variants. The results suggest that hydrogen peroxide and environmental conditions specific to biofilms are responsible for the development of non-phase-variable colony variants.
The Volatome of Aspergillus fumigatus (2014)

Early detection of invasive aspergillosis is absolutely required for efficient therapy of this fungal infection. The identification of fungal volatiles in patient breath can be an alternative for the detection of Aspergillus fumigatus that still remains problematic. In this work, we investigated the production of volatile organic compounds (VOCs) by A. fumigatus in vitro, and we show that volatile production depends on the nutritional environment. A. fumigatus produces a multiplicity of VOCs, predominantly terpenes and related compounds. The production of sesquiterpenoid compounds was found to be strongly induced by increased iron concentrations and certain drugs, i.e., pravastatin. Terpenes that were always detectable in large amounts were α-pinene, camphene, and limonene, as well as sesquiterpenes, identified as α-bergamotene and β-trans-bergamotene. Other substance classes that were found to be present in the volatome, such as 1-octen-3-ol, 3-octanone, and pyrazines, were found only under specific growth conditions. Drugs that interfere with the terpene biosynthesis pathway influenced the composition of the fungal volatome, and most notably, a block of sesquiterpene biosynthesis by the bisphosphonate alendronate fundamentally changed the VOC composition. Using deletion mutants, we also show that a terpene cyclase and a putative kaurene synthase are essential for the synthesis of volatile terpenes by A. fumigatus. The present analysis of in vitro volatile production by A. fumigatus suggests that VOCs may be used in the diagnosis of infections caused by this fungus.
Toward a Ferrous Iron-Cleavable Linker for Antibody–Drug Conjugates (2018)

Antibody-drug conjugates (ADCs) are antigen-targeted therapeutics that employ antibodies to deliver potent, cytotoxic effectors to cells with potentially high specificity. While promising clinical results have been achieved, significant pitfalls remain including internalization of ADCs in nontargeted cells expressing target antigen, which can limit therapeutic windows. Novel ADC linkers that are cleaved selectively in cancer cells but not in normal cells could minimize collateral damage caused by ADC uptake in nontargeted tissues. Here, we describe a prototypical ADC linker based on an Fe(II)-reactive 1,2,4-trioxolane scaffold (TRX) that by itself has demonstrated tumor-selective activity in preclinical cancer models. We prepared TRX-linked ADCs by site-selective conjugation to two sites in trastuzumab and compared their activity in Her2 positive and negative cells to ADC controls based on established linker chemistry. Our results confirm that the TRX moiety efficiently releases its payload following ADC uptake, affording picomolar potencies in antigen-positive cells. We also identified a destabilizing interaction between these initial TRX linkers and nearby antibody residues and suggest an approach to improve upon these prototypical designs.
Close Association of the First and Fourth Extracellular Domains of the Duffy Antigen/Receptor for Chemokines by a Disulfide Bond Is Required for Ligand Binding (1997)

It has been demonstrated that the promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines (DARC) is given by its extracellular NH2-terminal region. However, the relationship among the Fy6, Fya/b, and Fy3 epitopes, localized in the first and fourth extracellular domains of DARC, respectively, and the chemokine binding sites remained a matter of controversy. Here, we performed cross-displacement and cross-inhibition experiments indicating that all anti-Fy6, anti-Fya, and anti-Fy3 monoclonal antibodies and interleukin 8 are antagonists for binding to red cells. Biopanning of phage peptide libraries with an anti-Fy6 monoclonal antibody led to the identification of the motif Phe22-Glu23, the mutation of which altered the binding of both anti-Fy6 and chemokines (interleukin 8, MGSA, RANTES (regulated on activation normal T cell expressed)) to DARC transfectants. These results characterized the core of the Fy6 epitope and provided definitive proof of the tight relationship between Fy6 and the chemokine receptor site. Analysis of red cells treated by sulfhydryl group-modifying reagents suggested that the chemokine receptor function of DARC required the integrity of disulfide bond(s) but not that of free sulfhydryl group(s). Accordingly, mutation of cysteines 51 and 276 abolished chemokine binding to DARC transfectants. Altogether, our results suggested that the chemokine binding pocket of DARC included sequences located in the first and fourth extracellular domains which are brought into close vicinity by a disulfide bridge.
BGS Library: A Library Framework for Algorithms Evaluation in Foreground/Background Segmentation (2014)

International audience
Comparison of the WGEN and LARS-WG stochastic weather generators for diverse climates (1998)

Stochastic weather generators are used in a wide range of studies, such as hydrological applications, environmental management and agricultural risk assessments.Such studies often require long series of daily weather data for risk assessment and weather generators can produce time series of synthetic daily weather data of any length.Weather generators are also used to interpolate observed data to produce synthetic weather data at new sites, and they have recently been employed in the construction of climate change scenarios.Any generator should be tested to ensure that the data that it produces is satisfactory for the purposes for which it is to be used.The accuracy required will depend on the application of the data, and the performance of the generator may vary considerably for different climates.The aim of this paper is to test and compare 2 commonly-used weather generators, namely WGEN and LARS-WG, at 18 sites in the USA, Europe and Asia, chosen to represent a range of climates.Statistical tests were selected to compare a variety of different weather characteristics of the observed and synthetic weather data such as, for example, the lengths of wet and dry series, the distribution of precipitation and the lengths of frost spells.The LARS-WG generator used more complex distributions for weather variables and tended to match the observed data more closely than WGEN, although there are certain characteristics of the data that neither generator reproduced accurately.The implications for the development and use of stochastic weather generators are discussed.
FPGA-based parallel ASIP architecture for reactivesystems (1997)

A scalable parallel ASIP architecture based on FPGAs suitable for the implementation of reactive systems is described. The specification language used is extended statecharts. An industrial example requiring the real-time control of several stepper motors illustrates the benefits of the approach.
Parents’ experiences of living through their child's suffering from and surviving severe meningococcal disease (2005)

The aim of this study was to describe the lived experience of parents whose child had suffered from and survived severe meningococcal disease. A Heideggerian phenomenological approach was used within the study and data were collected from long focused interviews. In total, eight parents took part in the study; one was a woman recruited as a pilot interview and the other seven were recruited for the main study. The data were analysed using Colaizzi's (1978) method. Eleven themes emerged: (1) complications/side effects; (2) emotional turmoil; (3) child's physical appearance; (4) family disruption; (5) fear of death; (6) loss of parenting role; (7) need for support and understanding; (8) need and value of communication, information and publicity; (9) parental intuition; (10) technological interventions and (11) the impact of care delivery. A review of the literature arising out of the data was undertaken, and a final synthesis statement as perceived by the parents was achieved. Living through this experience is perceived as a major emotional stressor, and although health professionals have some insight into the experience, they are largely naive to the enormity of the situation.
Two for Typing: Homogeneous Combined Single-Nucleotide Polymorphism Scanning and Genotyping (2005)

More than 20 years after the first in vitro amplification of DNA by PCR, this technique is firmly established for diagnostic purposes in many clinical laboratories. PCR technology is an exciting field that has continually advanced. Evolutionary steps have been, for example, the transition from conventional cycling to rapid-cycling (1), from post-PCR to real-time product analysis (2), and from gel-based to probe-based PCR product identification (3) and genotyping with energy transfer probes (4).

One of the many possible applications of PCR in the clinical laboratory is genotyping. In this issue of Clinical Chemistry , Zhou et al., from Carl Wittwer’s group (5), contribute another innovation to this field. Their study reports a homogeneous technique based on simultaneous high-resolution melting of a whole PCR product and an unlabeled probe in the presence of saturating fluorescent DNA dye. It appears as the logical continuation of underlying previous work.

The use of fluorescence resonance energy transfer probe pairs for genotyping by analysis of the melting curve of a probe covering the mutation site was followed by hundreds of published applications since its first description (4). Single-nucleotide polymorphisms (SNPs) under a probe affect probe melting. The degree of destabilization depends on the type of SNP itself and on the bases that lie next to the SNP. By using a nearest-neighbor model, the melting temperatures of matched and mismatched probes can be predicted …
Multiuser diffuse indoor wireless infrared communication using equalized synchronous CDMA (2006)

We propose an indoor wireless infrared downlink scheme for high-data-rate multiuser connectivity with diffuse channels. The scheme is based on synchronous code-division multiple access with unipolar Hadamard codes. The orthogonality of unipolar Hadamard codes enables multiuser operation with relatively short codes. Thus, practical downlink rates of tens of Mb/s for each user can be obtained. However, multipath reflections in diffuse channels cause strong multipath dispersion and, consequently, severe distortion. This distortion becomes even more severe in a multiuser environment, as the dispersed incoherent infrared radiation of all users aggregates together. To mitigate this distortion, we use a novel adaptive multilevel serial composite decision feedback and feedforward equalizer. We investigate the system's performance with the proposed equalizer, and compare it with the performance of the same system, both composite decision-feedback and feedforward equalizers, and with a conventional decision-feedback equalizer (DFE). Our results show that the proposed scheme enables a high-data-rate multiaccess link and eliminates most of the multiuser distortion. Furthermore, it improves system performance in a multiaccess environment, as compared with the other composite equalizers and DFE for the same complexity. We also compare other coding schemes, and show that Hadamard codes are on top of the other codes
Probing Molecules in Confined Space (2011)

Despite the plethora of information regarding cellular crowding and its importance on modulating protein function the effects of confinement on biological molecules are often overlooked when investigating their physiological function. Recently however, the encapsulation of biomolecules in solid state matrices (NafionTM, sol-gels, zirconium phosphate,etc.) has increased in importance as a method for examining protein conformation and dynamics in confined space as well as novel applications in biotechnology. Biotechnological applications include, but are not limited to, bioremediation, biosensors, biocatalysts, etc. In order to better utilize solid state materials as substrates for biological molecules an understanding of the effects of encapsulation on the detailed dynamics associated with physiological function is required as well as a complete characterization of the physical properties associated with the space in which the biological molecule is to be confined. The focus of this research is to probe the effects of confinement on the thermodynamics of ligand photo-release/rebinding to the prototypical heme protein, myoglobin, encapsulated within sol-gel glasses utilizing photoacoustic calorimetry (PAC) and photothermal beam deflection (PBD). Optical spectroscopies (including optical absorption and fluorescence) have also been employed to characterize the molecular environments of materials including Zr-phosphate and metal organic polyhedral (MOPs), thought to be good candidates for novel bio-hybrid materials. The assembly mechanisms associated with MOPs were also examined in order to develop a foundation through which new, bio-compatible MOPs can be designed. Overall the results presented here represent a technological breakthrough in the application of fast calorimetry to the study of proteins in confined space. This will allow for the first time the acquisition of detailed thermodynamic maps associated with the well-choreographed biomolecular dynamics in confined environments.
File structures using hashing functions (1970)

A general method of file structuring is proposed which uses a hashing function to define tree structure. Two types of such trees are examined, and their relation to trees studied in the past is explained. Results for the probability distributions of path lengths are derived and illustrated.
Involvement ofINK4A gene products in the pathogenesis and development of human osteosarcoma (2001)

The current results suggest that, in OS, the altered expression of INK4A products plays a primary role in the deregulation of both pRb and p53 cell growth control pathways, contributing to tumor pathogenesis and development.