gebhart/patrepeval huggingface dataset:
Identification of novel dipeptidyl peptidase 9 substrates by two‐dimensional differential in‐gel electrophoresis (2015)

Dipeptidyl peptidase 9 (DPP9) is a member of the S9B/DPPIV (DPP4) serine protease family, which cleaves N-terminal dipeptides at an Xaa-Pro consensus motif. Cytoplasmic DPP9 has roles in epidermal growth factor signalling and in antigen processing, whilst the role of the recently discovered nuclear form of DPP9 is unknown. Mice lacking DPP9 proteolytic activity die as neonates. We applied a modified 2D differential in-gel electrophoresis approach to identify novel DPP9 substrates, using mouse embryonic fibroblasts lacking endogenous DPP9 activity. A total of 111 potential new DPP9 substrates were identified, with nine proteins/peptides confirmed as DPP9 substrates by MALDI-TOF or immunoblotting. Moreover, we also identified the dipeptide Val-Ala as a consensus site for DPP9 cleavage that was not recognized by DPP8, suggesting different in vivo roles for these closely related enzymes. The relative kinetics for the cleavage of these nine candidate substrates by DPP9, DPP8 and DPP4 were determined. This is the first identification of DPP9 substrates from cells lacking endogenous DPP9 activity. These data greatly expand the potential roles of DPP9 and suggest different in vivo roles for DPP9 and DPP8.
Dioxin Induces Localized, Graded Changes in Chromatin Structure: Implications for<i>Cyp1A1</i>Gene Transcription (1995)

In mouse hepatoma cells, the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) induces Cyp1A1 gene transcription, a process that requires two basic helix-loop-helix regulatory proteins, the aromatic hydrocarbon receptor (AhR) and the aromatic hydrocarbon receptor nuclear translocator (Arnt). We have used a ligation-mediated PCR technique to analyze dioxin-induced changes in protein-DNA interactions and chromatin structure of the Cyp1A1 enhancer-promoter in its native chromosomal setting. Dioxin-induced binding of the AhR/Arnt heteromer to enhancer chromatin is associated with a localized (about 200 bp) alteration in chromatin structure that is manifested by increased accessibility of the DNA; these changes probably reflect direct disruption of a nucleosome by AhR/Arnt. Dioxin induces analogous AhR/Arnt-dependent changes in chromatin structure and accessibility at the Cyp1A1 promoter. However, the changes at the promoter must occur by a different, more indirect mechanism, because they are induced from a distance and do not reflect a local effect of AhR/Arnt binding. Dose-response experiments indicate that the changes in chromatin structure at the enhancer and promoter are graded and mirror the graded induction of Cyp1A1 transcription by dioxin. We discuss these results in terms of a TCDD-induced shift in an equilibrium between nucleosomal and nonnucleosomal chromatin configurations.
Analysis of the Binding Site on Intercellular Adhesion Molecule 3 for the Leukocyte Integrin Lymphocyte Function-associated Antigen 1 (1995)

Intercellular adhesion molecule 3 (ICAM-3, CD50) is a member of the immunoglobulin superfamily and is a constitutively expressed ligand for the leukocyte integrin LFA-1 (CD11a/CD18). ICAM-3 is expressed at high levels by all resting leukocyte populations and antigen presenting cells and is a major ligand for LFA-1 in the resting immune system. ICAM-3 is a signal transducer and may play a key role in initiating immune responses. Mutant ICAM-3 Fc-chimeric proteins were quantitatively analyzed for their ability to bind COS cells expressing human LFA-1. The LFA-1-binding site on ICAM-3 is located in the N-terminal 2 Ig domains. Domains 3-5 do not significantly contribute to adhesion. The binding site has been further resolved by rational targeting of 14 point mutations throughout domains 1 and 2, coupled with modeling studies. Within domain 1 a cluster of residues (Glu37, Leu66, Ser68, and Gln75), that are predicted to lie on the CC'FG face of the Ig fold, play a dominant role in LFA-1 binding.
Apoptosis in plant disease response: A close encounter of the pathogen kind (2005)

In the present study pterygium excision combined with sliding conjunctival graft was a simplified surgical technique with a lower recurrence rate compared to the free conjunctival graft.
The binding of a novel bisheteroarylpiperazine mediates inhibition of human immunodeficiency virus type 1 reverse transcriptase. (1992)

The bisheteroarylpiperazines (BHAPs) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and specifically block HIV-1 replication (Romero, D. L., Busso, M., Tan, C.-K., Reusser, F., Palmer, J. R., Poppe, S. M., Aristoff, P. A., Downey, K. M., So, A. G., Resnick, L., and Tarpley, W. G. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 8806-8810). Here we show that the radiolabeled BHAP [3H]U-88204 binds specifically to HIV-1 RT with high affinity (KD of 50 nM) and a stoichiometry of 1 mol of U-88204 per 1 mol of p66/p51 RT heterodimer. Binding of [3H]U-88204 to RT is unaffected by the presence of saturating poly(rC).oligo (dG)12-18 template-primer. Direct measurement of competition between [3H]U-88204 and other RT inhibitors for binding to RT reveals mutually exclusive competition between [3H]U-88204 and the non-nucleoside RT inhibitor BI-RG-587 (Kopp, E. B., Miglietta, J. J., Shrutkowski, A. G., Shih, C.-K., Grob, P. M. and Skoog, M.T. (1991) Nucleic Acids Res. 19, 3035-3039), indicating that both share the same binding site. Phosphonoformate in concentrations up to 50 microM shows no competition with [3H]U-88204 for binding to RT either alone or in the presence of template-primer. Dideoxynucleotide RT inhibitors affect the binding of [3H]U-88204 to RT when complementary template-primer is present. [3H]U-88204 and the dideoxynucleotide ddGTP can bind RT simultaneously, but the presence of one ligand decreases the affinity of RT for the second. Inasmuch as ddGTP approximates the nucleotide substrate of RT, the direct demonstration of an RT-dideoxynucleotide-[3H]U-88204 complex validates the use of indirect kinetic methods to assess the strength of BHAP interaction with RT and suggests that RT inhibition by U-88204 is achieved via effects on nucleotide substrate binding.
The Utility of Supertype Clustering in Prediction for Class II MHC-Peptide Binding (2018)

We developed a new method, called superMHC, for class II MHC-peptide binding prediction, including three MHC isotypes of HLA-DR, HLA-DP, and HLA-DQ, by using supertype clustering in conjunction with RLS regression. The supertypes were identified by using a novel repertoire dissimilarity index to quantify the difference in MHC binding specificities. The superMHC method achieves the state-of-the-art performance and is demonstrated to predict binding affinities to a series of MHC molecules with few binders accurately. These results have implications for understanding receptor-ligand interactions involved in MHC-peptide binding.
Application of the Linked Data Visualization Model on Real World Data from the Czech LOD Cloud. (2014)

In the recent years the Linked Open Data phenomenon has gained a substantial traction. This has lead to a vast amount of data being available on the Web in what is known as the LOD cloud. While the potential of this linked data space is huge, it fails to reach the non-expert users so far. At the same time there is even larger amount of data that is so far not open yet, often because its owners are not convinced of its usefulness. In this paper we refine our Linked Data Visualization Model (LDVM) and show its application via its implementation Payola. On a real-world scenario built on real-world Linked Open Data created from Czech open data sources we show how end-user friendly visualizations can be easily achieved. Our first goal is to show that using Payola, existing Linked Open Data can be easily mashed up and visualized using an extensible library of analyzers, transformers and visualizers. Our second goal is to give po-tential publishers of (Linked) Open Data a proof that simply by publishing their data in a right way can bring them pow-erful visualizations at virtually no additional cost.
Comparing the Demands of Destination Entry using Google Glass and the Samsung Galaxy S4 (2014)

A driving simulation study assessed the impact of vocally entering an alpha numeric destination into Google Glass relative to voice and touch-entry methods using a handheld Samsung Galaxy S4 smartphone. Driving performance (standard deviation of lateral lane position and longitudinal velocity) and reaction to a light detection response task (DRT) were recorded for a gender-balanced sample of 24 young adult drivers. Task completion time and subjective workload ratings were also measured. Using Google Glass for destination entry had a statistically higher miss rate than using the Samsung Galaxy S4 voice interface, the Google Glass method took less time to complete, and the two methods were given comparable workload ratings by participants. In agreement with previous work, both voice interfaces performed significantly better than touch entry; this was seen in workload ratings, task duration, lateral lane control, and DRT metrics. Finally, irrespective of device or modality, destination entry significantly decreased responsiveness to events in the forward scene (as measured by the DRT reaction time) as compared to the baseline driving.
Multi-Task Video Captioning with Video and Entailment Generation (2017)

Video captioning, the task of describing the content of a video, has seen some promising improvements in recent years with sequence-to-sequence models, but accurately learning the temporal and logical dynamics involved in the task still remains a challenge, especially given the lack of sufficient annotated data. We improve video captioning by sharing knowledge with two related directed-generation tasks: a temporally-directed unsupervised video prediction task to learn richer context-aware video encoder representations, and a logically-directed language entailment generation task to learn better video-entailing caption decoder representations.
Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women (2005)

The compliance of large elastic arteries in the cardiothoracic region decreases with advancing age/menopause and plays an important role in the increased prevalence of cardiovascular diseases in postmenopausal women. We determined whether oxidative stress contributes to the reduced large elastic artery compliance of postmenopausal women. Carotid artery compliance was measured during acute intravenous infusions of saline (baseline control) and supraphysiological doses of the potent antioxidant ascorbic acid in premenopausal (n=10; 23+/-1; mean+/-SE) and estrogen-deficient postmenopausal (n=21; 55+/-1 years) healthy sedentary women. Carotid artery compliance was 56% lower in postmenopausal compared with premenopausal women during baseline control (P<0.0001). Ascorbic acid infusion increased carotid artery compliance by 26% in postmenopausal women (1.11+/-0.07 to 1.38+/-0.08 mm2/mm Hgx10(-1); P<0.001) but had no effect in premenopausal women (2.50+/-0.25 versus 2.43+/-0.20 mm2/mm Hgx10(-1)). Carotid artery diameter, blood pressure, and heart rate were unaffected by ascorbic acid. In the pooled population, the change in arterial compliance with ascorbic acid correlated with baseline waist-to-hip ratio (r=0.56; P=0.001), plasma norepinephrine (r=0.58; P=0.001), and LDL cholesterol (r=0.54; P=0.001). These results suggest that oxidative stress may be an important mechanism contributing to the reduced large elastic artery compliance of sedentary, estrogen-deficient postmenopausal women. Increased abdominal fat storage, sympathetic nervous system activity, and LDL cholesterol may be mechanistically involved in oxidative stress-associated suppression of arterial compliance in postmenopausal women.
Genistein inhibits growth of B16 melanoma cellsin vivo andin vitro and promotes differentiationin vitro (1997)

Consumption of soy products has been linked to a reduced mortality and morbidity from a number of cancers. Genistein, one of the principal soy isoflavones, has been shown to inhibit the growth of a number of tumour cell lines in vitro; however, a role of genistein in retarding tumour growth in vivo is less well documented. In this study, in addition to examining the effects of genistein on the growth of murine B16 melanoma cells in vitro, we have examined the effects of feeding a genistein-rich diet on s.c. growth of these tumour cells in mice. In vitro, the melanoma cells showed an increase in sensitivity to genistein with increasing time of exposure, culminating in a 50% growth inhibition (IC50) at 12.5 μM after 7 days. Genistein at 25 μM induced micronucleus formation after 24 hr and at concentrations as low as 2.5 μM induced morphological changes indicative of differentiation. Growth of solid tumours implanted into female C57BL/6J mice was inhibited by 50% when mice were fed genistein for 1 week before and for 1 week after inoculation with B16 melanoma cells. Plasma genistein concentrations at the time of tumour removal were 1.1 μM, which is similar to levels reported in humans consuming diets high in soybeans or soybean products, while control animals had no detectable genistein in plasma. Our results provide additional in vivo evidence suggesting that genistein retards the growth of implanted tumours, adding further to studies suggesting that this isoflavonoid is a biologically active component of soy foods. Int. J. Cancer 72:860–864, 1997. © 1997 Wiley-Liss, Inc.
Analysis and Simulation of a Digital Mobile Channel Using Orthogonal Frequency Division Multiplexing (1985)

This paper discusses the analysis and simulation of a technique for combating the effects of multipath propagation and cochannel interference on a narrow-band digital mobile channel. This system uses the discrete Fourier transform to orthogonally frequency multiplex many narrow subchannels, each signaling at a very low rate, into one high-rate channel. When this technique is used with pilot-based correction, the effects of flat Rayleigh fading can be reduced significantly. An improvement in signal-to-interference ratio of 6 dB can be obtained over the bursty Rayleigh channel. In addition, with each subchannel signaling at a low rate, this technique can provide added protection against delay spread. To enhance the behavior of the technique in a heavily frequency-selective environment, interpolated pilots are used. A frequency offset reference scheme is employed for the pilots to improve protection against cochannel interference.
Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma (2002)

In vitro studies suggest that resistance to chemotherapy-induced apoptosis might explain poor response to therapy in fatal cases. Actual execution of apoptosis depends on proper functioning of effector caspases, particularly caspase 3, and on the expression levels of apoptosis-regulating proteins, including Bcl-2 and the recently identified granzyme B- specific protease inhibitor 9 (PI9). Thus, high levels of caspase 3 activation should reflect proper functioning of the apoptosis pathways, resulting in chemotherapy-sensitive neoplastic cells and a favorable prognosis. We tested this hypothesis by quantifying numbers of tumor cells positive for active caspase 3, Bcl-2, and PI9, respectively, in pretreatment biopsies of systemic anaplastic large cell lymphoma (ALCL) patients and by comparing these numbers with clinical outcome. Activation of caspase 3 in more than 5% of the tumor cells was strongly correlated with a highly favorable outcome. High numbers of Bcl-2- and PI9-positive tumor cells were found to predict unfavorable prognosis. This prognostic effect was strongly related to anaplastic lymphoma kinase (ALK) status: ALK-positive ALCL had significantly higher levels of active caspase 3, while high expression of the antiapoptotic proteins Bcl-2 and PI9 was almost completely restricted to ALK-negative cases. In conclusion, high numbers of active caspase 3-positive tumor cells predict a highly favorable prognosis in systemic ALCL patients. Poor prognosis is strongly related to high numbers of Bcl-2- and PI9-positive neoplastic cells. These data support the notion that a favorable response to chemotherapy depends on an intact apoptosis cascade. Moreover, these data indicate that differences in prognosis between ALK-positive and ALK-negative ALCL might be explained by differences in expression of apoptosis-inhibiting proteins.
Diagnostic Performance of Digital versus Film Mammography for Breast-Cancer Screening (2005)

The overall diagnostic accuracy of digital and film mammography as a means of screening for breast cancer is similar, but digital mammography is more accurate in women under the age of 50 years, women with radiographically dense breasts, and premenopausal or perimenopausal women. (ClinicalTrials.gov number, NCT00008346.)
A Dynamic Model for Requirements Planning with Application to Supply Chain Optimization (1998)

This paper develops a new model for studying requirements planning in multistage production-inventory systems. We first characterize how most industrial planning systems work, and we then develop a mathematical model to capture some of the key dynamics in the planning process. Our approach is to use a model for a single production stage as a building block for modeling a network of stages. We show how to analyze the single-stage model to determine the production smoothness and stability for a production stage and the inventory requirements. We also show how to optimize the tradeoff between production capacity and inventory for a single stage. We then can model the multistage supply chain using the single stage as a building block. We illustrate the multistage model with an industrial application, and we conclude with some thoughts on a research agenda.
On calibrating measurements of packet transit times (1998)

We discuss the problem of detecting errors in measurements of the total delay experienced by packets transmitted through a wide-area network. We assume that we have measurements of the transmission times of a group of packets sent from an originating host, A, and a corresponding set of measurements of their arrival times at their destination host, B, recorded by two separate clocks. We also assume that we have a similar series of measurements of packets sent from B to A (as might occur when recording a TCP connection), but we do not assume that the clock at A is synchronized with the clock at B, nor that they run at the same frequency. We develop robust algorithms for detecting abrupt adjustments to either clock, and for estimating the relative skew between the clocks. By analyzing a large set of measurements of Internet TCP connections, we find that both clock adjustments and relative skew are sufficiently common that failing to detect them can lead to potentially large errors when analyzing packet transit times. We further find that synchronizing clocks using a network time protocol such as NTP does not free them from such errors.
An initial investigation into non-visual computer supported collaboration (2007)

In this paper we present an initial study of computer supported collaboration between visually impaired users based around the interactive browsing and manipulation of simple graphs. We specifically looked at supporting awareness of others activities and interaction between participants. We found that shared audio and haptic locating tools, to allow users to find each other, are useful. However further work is required to determine the general applicability of our findings.
The WebBook and the Web Forager (1996)

The World-Wide Web has achieved global connectivity stimulating the transition of computers from knowledge processors to knowledge sources. But the Web and its client software are seriously deficient for supporting users' interactive use of this information. This paper presents two related designs with which to evolve the Web and its clients. The first is the WebBook, a 3D interactive book of HTML pages. The WebBook allows rapid interaction with objects at a higher level of aggregation than pages. The second is the Web Forager, an application that embeds the WebBook and other objects in a hierarchical 3D workspace, Both designs are intended as exercises to play off against analytical studies of information workspaces.
Assessing the colloidal properties of engineered nanoparticles in water: case studies from fullerene C60 nanoparticles and carbon nanotubes (2010)

Environmental context. The fate and bioavailability of engineered nanoparticles in natural aquatic systems are strongly influenced by their ability to remain dispersed in water. Consequently, understanding the colloidal properties of engineered nanoparticles through rigorous characterisation of physicochemical properties and measurements of particle stability will allow for a more accurate prediction of their environmental, health, and safety effects in aquatic systems. This review highlights some important techniques suitable for the assessment of the colloidal properties of engineered nanoparticles and discusses some recent findings obtained by using these techniques on two popular carbon-based nanoparticles, fullerene C60 and multi-walled carbon nanotubes. Abstract. The colloidal properties of engineered nanoparticles directly affect their use in a wide variety of applications and also control their environmental fate and mobility. The colloidal stability of engineered nanoparticles depends on their physicochemical properties within the given aqueous medium and is ultimately reflected in the particles’ aggregation and deposition behaviour. This review presents some of the key experimental methods that are currently used to probe colloidal properties and quantify engineered nanoparticle stability in water. Case studies from fullerene C60 nanoparticles and multi-walled carbon nanotubes illustrate how the characterisation and measurement methods are used to understand and predict nanoparticle fate in aquatic systems. Consideration of the comparisons between these two classes of carbon-based nanoparticles provides useful insights into some major current knowledge gaps while also revealing clues about needed future developments. Key issues to be resolved relate to the nature of near-range surface forces and the origins of surface charge, particularly for the reportedly unmodified or ‘pure’ carbon-based nanoparticles.
Basal Subtype and MAPK/ERK Kinase (MEK)-Phosphoinositide 3-Kinase Feedback Signaling Determine Susceptibility of Breast Cancer Cells to MEK Inhibition (2009)

Specific inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We used a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understand molecular mechanisms conferring resistance to such compounds. Basal-type breast cancer cells were found to be particularly susceptible to growth inhibition by small-molecule MEK inhibitors. Activation of the phosphatidylinositol 3-kinase (PI3K) pathway in response to MEK inhibition through a negative MEK-epidermal growth factor receptor-PI3K feedback loop was found to limit efficacy. Interruption of this feedback mechanism by targeting MEK and PI3K produced synergistic effects, including induction of apoptosis and, in some cell lines, cell cycle arrest and protection from apoptosis induced by proapoptotic agents. These findings enhance our understanding of the interconnectivity of oncogenic signal transduction circuits and have implications for the design of future clinical trials of MEK inhibitors in breast cancer by guiding patient selection and suggesting rational combination therapies.