gebhart/patrepeval huggingface dataset:
Prevalence of BRCA1 in a hospital-based population of Dutch breast cancer patients. (1999)

Summary The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch breast cancer patients not selected for family history or age at diagnosis. They were tested for germline mutations in the BRCA1 gene using an assay which detects small deletions and insertions (DSDI), as well as the two major genomic founder deletions present in the Dutch population. Data on family history and bilateral breast cancer were obtained retrospectively. Ten protein truncating mutations were detected and one in-frame deletion with an unknown relation to disease risk. Four patients carried the Dutch founder deletion of exon 22. Based on these results the estimated prevalence of breast cancer in the general population in the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age and under 50 years-of-age this prevalence is 9.5 % and 6.4%, respectively. All mutation carriers were under 50 years-of-age at diagnosis of the first breast cancer, and five did not have any relative with breast cancer. The proportions of bilateral breast cancer in the mutation carriers and noncarriers did not differ from each other. These data indicate that in the general Dutch breast cancer population the great majority of BRCA1 mutations will be found in women diagnosed under 50 years-of-age. © 2000 Cancer Research Campaign
On the Quantification of Global Team Performance and Profitability (2014)

Globalization helps international companies create distinct competitive and operational advantages over centrally managed counterparts. Such advantages come from increased business opportunity and high profitability through outsourcing. To achieve the benefits of outsourcing, in this paper we describe a general model that characterizes globalized project productivity. We examine several factors related to global team performance including: 1) time zone differences, 2) language difference, 3) working time alignment (such as vacations and holidays), and 4) turnover rates among skilled workers in expanding economies. We then show how the models can be used to analyze project profitability through team performance, and how to address the combined impact of multiple globalization factors. Beyond this, we also provide suggestions on how to overcome those challenges. The key contribution of this paper is the development of models that quantify the impact of several global factors. In two cases, we show that the right organizational structure is required to achieve benefits of lower labor costs. In another case, due to the smaller difference in labor costs and the high complexity of the project, we show that the combined effects of the factors could lead to reduced profitability. It is these cases that reveal there is an opportunity to improve global delivery. Our objective is to show how to maximize the benefits of globalization and how an effective management approach can avoid some of the potential risks by deeply understanding the effects of global factors.
Multilocus Sequence Typing and Virulence Gene Profiles Associated with Escherichia coli from Human and Animal Sources (2015)

We investigated whether specific sequence types, and their shared virulence gene profiles, may be associated with both human and food animal reservoirs. A total of 600 Escherichia coli isolates were assembled from human (n=265) and food-animal (n=335) sources from overlapping geographic areas and time periods (2005–2010) in Canada. The entire collection was subjected to multilocus sequence typing and a subset of 286 E. coli isolates was subjected to an E. coli–specific virulence gene microarray. The most common sequence type (ST) was E. coli ST10, which was present in all human and food-animal sources, followed by ST69, ST73, ST95, ST117, and ST131. A core group of virulence genes was associated with all 10 common STs including artJ, ycfZ, csgA, csgE, fimA, fimH, gad, hlyE, ibeB, mviM, mviN, and ompA. STs 73, 92, and 95 exhibited the largest number of virulence genes, and all were exclusively identified from human infections. ST117 was found in both human and food-animal sources and shared virulence genes common in extraintestinal pathogenic E. coli lineages. Select groups of E. coli may be found in both human and food-animal reservoirs.
Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli (1999)

The involvement of dopamine neurotransmission in behavioral responses to novelty is suggested by reports that reward is related to increased dopamine activity, that dopamine modulates exploratory behavior in animals, and that Parkinson's disease patients report diminished responses to novelty. Some studies have reported that polymorphisms of the human dopamine D4 receptor (D4R) gene are associated with personality inventory measures of the trait called "novelty-seeking". To explore a potential role for the D4R in behavioral responses to novelty, we evaluated D4R-knock-out (D4R-/-) and wild-type (D4R+/+) mice in three approach-avoidance paradigms: the open field, emergence, and novel object tests. These three paradigms differ in the degree to which they elicit approach, or exploratory behavior, and avoidance, or anxiety-related behavior. Thus, we used these three tests to determine whether the D4R primarily influences the exploratory or the anxious component of responses to approach-avoidance conflicts. D4R-/- mice were significantly less behaviorally responsive to novelty than D4R+/+ mice in all three tests. The largest phenotypic differences were observed in the novel object test, which maximizes approach behavior, and the smallest phenotypic differences were found in the open field test, which maximizes avoidance behavior. Hence, D4R-/- mice exhibit reductions in behavioral responses to novelty, reflecting a decrease in novelty-related exploration.
PORTUGAL NA POESIA SATÍRICA DE JORGE DE SENA (2013)

Jorge de Sena&rsquo;s satire is an accusation worded in a language which is one of the richest and fullest in self-awareness of all the satirical poetry written in Portuguese. From this evidence, the essay moves into the analysis of the markedly intellectual meaning of a creation investing in the diversification of verbal styles, from the most erudite to the most colloquial and obscene, and in the coexistence of states of mind: melancholy and anger are brought together in a compound whose emphasis varies in accordance with the play of forces acting in the poem.
Cytostatic Effect of Deoxyspergualin on a Murine Leukemia Cell Line L1210 (1991)

The mode of antiproliferative action of deoxyspergualin (NKT-01) was examined. The growth-inhibitory effect on a murine leukemia cell line L1210 following treatment with NKT-01 was time-dependent, and there was little or no effect on the syntheses of DNA and RNA. Thus, the inhibitory activity of NKT-01 was not attributable to the inhibition of DNA and RNA syntheses. The influence of NKT-01 on cell cycle progression was studied by flow cytometric analysis. Bromodeoxyuridine/DNA distribution patterns in cells that were treated for 72 h, showed that the growth inhibition is due to the delay of cell cycle progression but not to cytotoxicity. This finding was also supported by evidence that the treated cells were re-proliferative in fresh medium. In addition, a majority of drug-treated cells was prevented from traversing from the G0/G1 phase to the S phase by 144 h or longer exposure to NKT-01. The results suggest that NKT-01 is cytostatic, preventing G0/G1-S progression.
A linear oscillator model predicts dynamic temporal attention and pupillary entrainment to rhythmic patterns (2018)

Rhythm is a ubiquitous feature of music that induces specific neural modes of processing. In this paper, we assess the potential of a stimulus-driven linear oscillator model (57) to predict dynamic attention to complex musical rhythms on an instant-by-instant basis. We use perceptual thresholds and pupillometry as attentional indices against which to test our model predictions. During a deviance detection task, participants listened to continuously looping, multiinstrument, rhythmic patterns, while being eye-tracked. Their task was to respond anytime they heard an increase in intensity (dB SPL). An adaptive thresholding algorithm adjusted deviant intensity at multiple probed temporal locations throughout each rhythmic stimulus. The oscillator model predicted participants' perceptual thresholds for detecting deviants at probed locations, with a low temporal salience prediction corresponding to a high perceptual threshold and vice versa. A pupil dilation response was observed for all deviants. Notably, the pupil dilated even when participants did not report hearing a deviant. Maximum pupil size and resonator model output were significant predictors of whether a deviant was detected or missed on any given trial. Besides the evoked pupillary response to deviants, we also assessed the continuous pupillary signal to the rhythmic patterns. The pupil exhibited entrainment at prominent periodicities present in the stimuli and followed each of the different rhythmic patterns in a unique way. Overall, these results replicate previous studies using the linear oscillator model to predict dynamic attention to complex auditory scenes and extend the utility of the model to the prediction of neurophysiological signals, in this case the pupillary time course; however, we note that the amplitude envelope of the acoustic patterns may serve as a similarly useful predictor. To our knowledge, this is the first paper to show entrainment of pupil dynamics by demonstrating a phase relationship between musical stimuli and the pupillary signal.
Heterogeneity and plasticity of epidermal stem cells (2014)

The epidermis is an integral part of our largest organ, the skin, and protects us against the hostile environment. It is a highly dynamic tissue that, during normal steady-state conditions, undergoes constant turnover. Multiple stem cell populations residing in autonomously maintained compartments facilitate this task. In this Review, we discuss stem cell behaviour during normal tissue homeostasis, regeneration and disease within the pilosebaceous unit, an integral structure of the epidermis that is responsible for hair growth and lubrication of the epithelium. We provide an up-to-date view of the pilosebaceous unit, encompassing the heterogeneity and plasticity of multiple discrete stem cell populations that are strongly influenced by external cues to maintain their identity and function.
An All-Digital True Random Number Generator Based on Chaotic Cellular Automata Topology (2019)

True random number generator (TRNG) is an important primitive in cryptographic applications. In this paper, a TRNG based on a self-timed ring structure is presented, the basic elements of the ring is a realization of a chaotic cellular automata topology. In particular, the proposed TRNG design is fully synthesizable with standard all-digital components. Test chips of the proposed TRNG structure were fabricated with 40nm TSMC technology node, and the utilized overhead is only 75 NAND gates equivalent, with a die area of 270 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Experimental results demonstrated that the TRNG test chips can generate random numbers at a high bit rate: 1600Mb/s. The test sequences generated by the TRNG test chips passed all test statistics of the widely used test suite: NIST SP800-22, as well as the independent and identically distributed (IID) test of NIST SP800-90B.
Clustering techniques for large data sets—from the past to the future (1999)

Application Example: Marketing – Given: • Large data base of customer data containing their properties and past buying records
Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis (1994)

Metastasis and tumor angiogenesis are invasive phenomena and share many common properties at the physiological level and some similarities at the molecular level. Each consists of repetitive cycles of interaction with adjacent extracellular matrix components by mediating cellular adhesion, matrix dissolution, and cellular motility to achieve metastasis of cancer cells or neovascularization of tumors. Molecular factors which implement this triad of events are reviewed, as are several signal transduction components which may regulate them. Some potentially promising prognostic, diagnostic, and therapeutic modalities for tumor angiogenesis and metastatic disease are also discussed.
Synergistic Activation of theN-Methyl-d-aspartate Receptor Subunit 1 Promoter by Myocyte Enhancer Factor 2C and Sp1 (1998)

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important roles in neuronal development, plasticity, and cell death. NMDA receptor subunit 1 (NR1) is an essential subunit of the NMDA receptor and is developmentally expressed in postnatal neurons of the central nervous system. Here we identify on the NR1 promoter a binding site for myocyte enhancer factor 2C (MEF2C), a developmentally expressed neuron/muscle transcription factor found in cerebrocortical neurons, and study its regulation of the NR1 gene. Co-expression of MEF2C and Sp1 cDNAs in primary neurons or cell lines synergistically activates the NR1 promoter. Disruption of the MEF2 site or the MEF2C DNA binding domain moderately reduces this synergism. Mutation of the Sp1 sites or the activation domains of Sp1 protein strongly reduces the synergism. Results of yeast two-hybrid and co-immunoprecipitation experiments reveal a physical interaction between MEF2C and Sp1 proteins. The MEF2C DNA binding domain is sufficient for this interaction. Dominant-negative MEF2C interferes with expression of NR1 mRNA in neuronally differentiated P19 cells. Growth factors, including epidermal growth factor and basic fibroblast growth factor, can up-regulate NR1 promoter activity in stably transfected PC12 cells, even in the absence of the MEF2 site, but the Sp1 sites are necessary for this growth factor regulation, suggesting that Sp1 sites may mediate these effects.
Early metabolomics changes in heart and plasma during chronic doxorubicin treatment in B6C3F1 mice (2016)

The present study aimed to identify molecular markers of early stages of cardiotoxicity induced by a potent chemotherapeutic agent, doxorubicin (DOX). Male B6C3F1 mice were dosed with 3 mg kg(-1) DOX or saline via tail vein weekly for 2, 3, 4, 6 or 8 weeks (cumulative DOX doses of 6, 9, 12, 18 or 24 mg kg(-1) , respectively) and euthanized a week after the last dose. Mass spectrometry-based and nuclear magnetic resonance spectrometry-based metabolic profiling were employed to identify initial biomarkers of cardiotoxicity before myocardial injury and cardiac pathology, which were not noted until after the 18 and 24 mg kg(-1) cumulative doses, respectively. After a cumulative dose of 6 mg kg(-1) , 18 amino acids and four biogenic amines (acetylornithine, kynurenine, putrescine and serotonin) were significantly increased in cardiac tissue; 16 amino acids and two biogenic amines (acetylornithine and hydroxyproline) were significantly altered in plasma. In addition, 16 acylcarnitines were significantly increased in plasma and five were significantly decreased in cardiac tissue compared to saline-treated controls. Plasma lactate and succinate, involved in the Krebs cycle, were significantly altered after a cumulative dose of 6 mg kg(-1) . A few metabolites remained altered at higher cumulative DOX doses, which could partly indicate a transition from injury processes at 2 weeks to repair processes with additional injury happening concurrently before myocardial injury at 8 weeks. These altered metabolic profiles in mouse heart and plasma during the initial stages of injury progression due to DOX treatment may suggest these metabolites as candidate early biomarkers of cardiotoxicity. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Synthesis of Poly(alkyl/arylphosphazenes) and Their Precursors (1994)

Poly(alkyl/arylphosphazenes), [R2P=N]n, are a class of phosphazene polymers in which all of the side groups are attached to the P-N backbone via direct phosphorus-carbon bonds. While other types of poly(phosphazenes) are usually prepared by the ring-opening polymerization of the cyclic trimer, [Cl2P=N]3, followed by nucleophilic substitution of the P-Cl groups along the polymer backbone, the poly(alkyl/arylphosphazenes) are directly obtained by the thermal condensation polymerization of N-silylphosphoranimines, Me3SiN=PR2X. This paper reviews (1) the overall scope and limitations of this condensation polymerization, (2) some general properties of the title polymers, (3) recent improvements in the synthetic methodology including catalysis of the polymerization process as well as simplification of the precursor synthesis, (4) observations relevant to the polymerization mechanism such as leaving group effects, and (5) the synthesis, structure, and reactivity of some related small molecule species including N-silylphosphoranimines with bulky silyl groups, acetylene-substituted Si-N-P systems, and new N-phosphoryl-phosphoranimines, e.g., Cl2P(O)-N=PR2X.
A new approach to categorization of radiologic inflammation in chronic rhinosinusitis (2020)

Chronic rhinosinusitis (CRS) is a prevalent condition. Clinical diagnosis requires subjective evidence (i.e. symptoms) and objective evidence of inflammation (e.g. sinus computed tomography [CT]). Few studies have assessed differences in common CT scoring approaches for CRS, the Lund-Mackay (LM) system and its modified version (mLM); none in a general population sample. The aims of this study were to answer the following: (1) Is mLM superior to LM? (2) Should nasal cavity opacification be included in scoring? (3) How should location-specific scores be utilized? (4) If location-specific scores are summed, what should be the cutoff? (5) Are associations of opacification with symptoms observed when using different measurement approaches? We scored sinus CTs using LM and mLM from 526 subjects selected from a larger CRS study. Exploratory factor analysis (EFA) assessed similarity of mLM and LM. Latent class analysis (LCA) identified subgroups of sinus opacification patterns. Factors associated with group membership and relations with nasal and sinus symptoms (NSS) guided clinical relevance. EFA suggested no differences between LM and mLM, or after addition of nasal cavity opacification. LCA identified three opacification groups: no/mild, localized, and diffuse. Males were 2.7x more likely to have diffuse opacification than females, as were those with asthma or hay fever. A LM cutoff of 3 had similar performance to the currently used 4. Diffuse opacification was associated with nasal blockage and smell loss. Differing patterns of opacification may be clinically relevant, improving measurement of objective evidence in studies of CRS and sinus diseases.
Systematic Investigation of Tether Length and Phosphorus Configuration in Backbone Constrained Macrocyclic Nucleic Acids to Modulate Binding Kinetics for RNA (2023)

We recently described a chemical strategy to pre-organize a trinucleotide subunit in a conformation suitable for Watson-Crick base pairing for modulating the binding kinetics of single-stranded oligonucleotides (ONs) using bis-phosphonate esters bridging hydrocarbon tethers to provide 11- and 15-membered macrocyclic analogues. In this manuscript, we describe the synthesis of all eight P-stereoisomers of macrocyclic 12-, 13-, 14-, and 16-membered hydrocarbon-bridged nucleotide trimers, their incorporation into ONs, and biophysical characterization of the modified ONs. The size of the macrocyclic tether and configuration at phosphorus had profound effects on hybridization kinetics. ONs containing 12- and 13-membered rings exhibited faster on-rates (up to 5-fold) and off-rates (up to 161-fold). In contrast, ONs using the larger ring size macrocycles generally exhibited smaller changes in binding kinetics relative to unmodified DNA. Interestingly, several of the analogues retained significant binding affinity for RNA based on their dissociation constants, despite being modestly destabilizing in the thermal denaturation experiments, highlighting the potential utility of measuring dissociation constants versus duplex thermal stability when evaluating novel nucleic acid analogues. Overall, our results provide additional insights into the ability of backbone-constrained macrocyclic nucleic acid analogues to modulate hybridization kinetics of modified ONs with RNA.
Deposition of Thick Wear and Corrosion Resistant Coatings by High Power Diode Laser (2006)

Abstract High power diode lasers (HPDL) at the level of ? 6 kW are efficient cladding tools in heavy engineering applications where thick (up to 5 mm) wear and corrosion resistant coating layers are required. Large beam geometry makes possible the overlap of thick 20 mm wide cladding tracks side by side without coating defects. Compact size and closed cooling water circulation enable HPDL cladding process to take place also at a site of new or worn high-value machine parts, which have worn in operation or been damaged already during overseas transportation. Instead of moving parts of several tons’ weight, it would be perhaps more cost efficient to transport HPDL cladding unit.
Applying Transition Networks in Translating (2003)

The paper presents an adoption of transition networks to recogniz­ ing and translating fragments of texts characteristic of e-mails written in Polish. An extension of XTND (XML Transition Networks Definition) - abbreviated as PTND - is introduced in order to provide a convenient way to describe these networks. A new tool for graphical representation, modification and validation of network descriptions is proposed.
Synthesis and Antisense Properties of 2′‐O‐(2S‐Methoxypropyl)‐RNA‐Modified Gapmer Antisense Oligonucleotides (2014)

To ascertain whether increasing hydrophobicity can enhance the activity of second-generation antisense oligonucleotides (ASOs) in muscle, we investigated the antisense properties of 2'-O-(2S-methoxypropyl)-RNA (2S-MOP)-modified ASOs. Synthesis of the 2S-MOP 5-methyl uridine phosphoramidite was accomplished on a multi-gram scale by Lewis-acid-catalyzed ring opening of 5'-O-tert-butyldiphenylsilyl ether-protected 2,2'-anhydro-5-methyl uridine with 2S-methoxy-1-propanol. Synthesis of the 2S-MOP 5-methyl cytidine nucleoside from the corresponding 5-methyl uridine nucleoside was accomplished by formation and displacement of a 4-triazolide intermediate with aqueous ammonia. 2S-MOP-modified oligonucleotides were prepared on an automated DNA synthesizer and showed similar enhancements in duplex thermal stability as 2'-O-methoxyethyl RNA (MOE)-modified oligonucleotides. 2S-MOP-containing antisense oligonucleotides were evaluated in Balb-c mice and showed good activity for decreasing the expression levels of scavenger receptor B1 (Srb1) and phosphatase and tensin homologue (PTEN) mRNA in liver and muscle tissue.
Subtoxic Oxidative Stress Induces Senescence in Retinal Pigment Epithelial Cells via TGF-β Release (2009)

Oxidative stress, TGF-beta1, and TGF-beta2 are capable of inducing cellular senescence in cultured human RPE cells. Therefore, reduction of oxidative stress and minimizing TGF-beta may help to prevent senescence-associated changes in the RPE as seen in early age-related macular degeneration.